@article {10775, title = {Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.}, journal = {Genome Biol}, volume = {19}, year = {2018}, month = {2018 07 17}, pages = {87}, abstract = {

BACKGROUND: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.

RESULTS: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874~individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.

CONCLUSIONS: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

}, keywords = {ADAMTS Proteins, African Continental Ancestry Group, Animals, Connexin 43, Electrocardiography, European Continental Ancestry Group, Exome, Female, Gene Expression, Gene Expression Profiling, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Humans, Male, Mice, Middle Aged, Myocardium, Open Reading Frames, Polymorphism, Single Nucleotide, Whole Exome Sequencing}, issn = {1474-760X}, doi = {10.1186/s13059-018-1457-6}, author = {Prins, Bram P and Mead, Timothy J and Brody, Jennifer A and Sveinbjornsson, Gardar and Ntalla, Ioanna and Bihlmeyer, Nathan A and van den Berg, Marten and Bork-Jensen, Jette and Cappellani, Stefania and Van Duijvenboden, Stefan and Klena, Nikolai T and Gabriel, George C and Liu, Xiaoqin and Gulec, Cagri and Grarup, Niels and Haessler, Jeffrey and Hall, Leanne M and Iorio, Annamaria and Isaacs, Aaron and Li-Gao, Ruifang and Lin, Honghuang and Liu, Ching-Ti and Lyytik{\"a}inen, Leo-Pekka and Marten, Jonathan and Mei, Hao and M{\"u}ller-Nurasyid, Martina and Orini, Michele and Padmanabhan, Sandosh and Radmanesh, Farid and Ramirez, Julia and Robino, Antonietta and Schwartz, Molly and van Setten, Jessica and Smith, Albert V and Verweij, Niek and Warren, Helen R and Weiss, Stefan and Alonso, Alvaro and Arnar, David O and Bots, Michiel L and de Boer, Rudolf A and Dominiczak, Anna F and Eijgelsheim, Mark and Ellinor, Patrick T and Guo, Xiuqing and Felix, Stephan B and Harris, Tamara B and Hayward, Caroline and Heckbert, Susan R and Huang, Paul L and Jukema, J W and K{\"a}h{\"o}nen, Mika and Kors, Jan A and Lambiase, Pier D and Launer, Lenore J and Li, Man and Linneberg, Allan and Nelson, Christopher P and Pedersen, Oluf and Perez, Marco and Peters, Annette and Polasek, Ozren and Psaty, Bruce M and Raitakari, Olli T and Rice, Kenneth M and Rotter, Jerome I and Sinner, Moritz F and Soliman, Elsayed Z and Spector, Tim D and Strauch, Konstantin and Thorsteinsdottir, Unnur and Tinker, Andrew and Trompet, Stella and Uitterlinden, Andr{\'e} and Vaartjes, Ilonca and van der Meer, Peter and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Waldenberger, Melanie and Wilson, James G and Xie, Zhijun and Asselbergs, Folkert W and D{\"o}rr, Marcus and van Duijn, Cornelia M and Gasparini, Paolo and Gudbjartsson, Daniel F and Gudnason, Vilmundur and Hansen, Torben and K{\"a}{\"a}b, Stefan and Kanters, J{\o}rgen K and Kooperberg, Charles and Lehtim{\"a}ki, Terho and Lin, Henry J and Lubitz, Steven A and Mook-Kanamori, Dennis O and Conti, Francesco J and Newton-Cheh, Christopher H and Rosand, Jonathan and Rudan, Igor and Samani, Nilesh J and Sinagra, Gianfranco and Smith, Blair H and Holm, Hilma and Stricker, Bruno H and Ulivi, Sheila and Sotoodehnia, Nona and Apte, Suneel S and van der Harst, Pim and Stefansson, Kari and Munroe, Patricia B and Arking, Dan E and Lo, Cecilia W and Jamshidi, Yalda} } @article {10444, title = {Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.}, journal = {Nat Genet}, volume = {50}, year = {2018}, month = {2018 Jun}, pages = {834-848}, abstract = {

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.

}, issn = {1546-1718}, doi = {10.1038/s41588-018-0127-7}, author = {Tedja, Milly S and Wojciechowski, Robert and Hysi, Pirro G and Eriksson, Nicholas and Furlotte, Nicholas A and Verhoeven, Virginie J M and Iglesias, Adriana I and Meester-Smoor, Magda A and Tompson, Stuart W and Fan, Qiao and Khawaja, Anthony P and Cheng, Ching-Yu and H{\"o}hn, Ren{\'e} and Yamashiro, Kenji and Wenocur, Adam and Grazal, Clare and Haller, Toomas and Metspalu, Andres and Wedenoja, Juho and Jonas, Jost B and Wang, Ya Xing and Xie, Jing and Mitchell, Paul and Foster, Paul J and Klein, Barbara E K and Klein, Ronald and Paterson, Andrew D and Hosseini, S Mohsen and Shah, Rupal L and Williams, Cathy and Teo, Yik Ying and Tham, Yih Chung and Gupta, Preeti and Zhao, Wanting and Shi, Yuan and Saw, Woei-Yuh and Tai, E-Shyong and Sim, Xue Ling and Huffman, Jennifer E and Polasek, Ozren and Hayward, Caroline and Bencic, Goran and Rudan, Igor and Wilson, James F and Joshi, Peter K and Tsujikawa, Akitaka and Matsuda, Fumihiko and Whisenhunt, Kristina N and Zeller, Tanja and van der Spek, Peter J and Haak, Roxanna and Meijers-Heijboer, Hanne and van Leeuwen, Elisabeth M and Iyengar, Sudha K and Lass, Jonathan H and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Vingerling, Johannes R and Lehtim{\"a}ki, Terho and Raitakari, Olli T and Biino, Ginevra and Concas, Maria Pina and Schwantes-An, Tae-Hwi and Igo, Robert P and Cuellar-Partida, Gabriel and Martin, Nicholas G and Craig, Jamie E and Gharahkhani, Puya and Williams, Katie M and Nag, Abhishek and Rahi, Jugnoo S and Cumberland, Phillippa M and Delcourt, C{\'e}cile and Bellenguez, C{\'e}line and Ried, Janina S and Bergen, Arthur A and Meitinger, Thomas and Gieger, Christian and Wong, Tien Yin and Hewitt, Alex W and Mackey, David A and Simpson, Claire L and Pfeiffer, Norbert and P{\"a}rssinen, Olavi and Baird, Paul N and Vitart, Veronique and Amin, Najaf and van Duijn, Cornelia M and Bailey-Wilson, Joan E and Young, Terri L and Saw, Seang-Mei and Stambolian, Dwight and MacGregor, Stuart and Guggenheim, Jeremy A and Tung, Joyce Y and Hammond, Christopher J and Klaver, Caroline C W} } @article {10426, title = {A genome-wide association study of corneal astigmatism: The CREAM Consortium.}, journal = {Mol Vis}, volume = {24}, year = {2018}, month = {2018}, pages = {127-142}, abstract = {

Purpose: To identify genes and genetic markers associated with corneal astigmatism.

Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression.

Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha () gene: top SNP: rs7673984, odds ratio=1.12 (95\% CI:1.08-1.16), p=5.55{\texttimes}10. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (), acid phosphatase 2, lysosomal (), and TNF alpha-induced protein 8 like 3 ().

Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the gene, gene-based analysis identified three novel candidate genes, , , and , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

}, keywords = {Acid Phosphatase, Asian Continental Ancestry Group, Astigmatism, Claudins, Cohort Studies, Cornea, Corneal Diseases, European Continental Ancestry Group, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Odds Ratio, Polymorphism, Single Nucleotide, Receptor, Platelet-Derived Growth Factor alpha, Software}, issn = {1090-0535}, author = {Shah, Rupal L and Li, Qing and Zhao, Wanting and Tedja, Milly S and Tideman, J Willem L and Khawaja, Anthony P and Fan, Qiao and Yazar, Seyhan and Williams, Katie M and Verhoeven, Virginie J M and Xie, Jing and Wang, Ya Xing and Hess, Moritz and Nickels, Stefan and Lackner, Karl J and P{\"a}rssinen, Olavi and Wedenoja, Juho and Biino, Ginevra and Concas, Maria Pina and Uitterlinden, Andr{\'e} and Rivadeneira, Fernando and Jaddoe, Vincent W V and Hysi, Pirro G and Sim, Xueling and Tan, Nicholas and Tham, Yih-Chung and Sensaki, Sonoko and Hofman, Albert and Vingerling, Johannes R and Jonas, Jost B and Mitchell, Paul and Hammond, Christopher J and H{\"o}hn, Ren{\'e} and Baird, Paul N and Wong, Tien-Yin and Cheng, Chinfsg-Yu and Teo, Yik Ying and Mackey, David A and Williams, Cathy and Saw, Seang-Mei and Klaver, Caroline C W and Guggenheim, Jeremy A and Bailey-Wilson, Joan E} } @article {10463, title = {CCR5Δ32 and the genetic susceptibility to rheumatoid arthritis in admixed populations: a multicentre study.}, journal = {Rheumatology (Oxford)}, volume = {56}, year = {2017}, month = {2017 03 01}, pages = {495-497}, keywords = {Arthritis, Rheumatoid, Brazil, Case-Control Studies, Consanguinity, Gene Frequency, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Receptors, CCR5}, issn = {1462-0332}, doi = {10.1093/rheumatology/kew398}, author = {Toson, Bruno and Dos Santos, Eduardo Jos{\'e} and Adelino, Jos{\'e} Eduardo and Sandrin-Garcia, Paula and Crovella, Sergio and Louzada-J{\'u}nior, Paulo and Oliveira, Ren{\^e} Donizete Ribeiro and Pedroza, Larysse Santa Rosa Aquino and de F{\'a}tima Lobato Cunha Sauma, Maria and de Lima, Clayton Pereira Silva and Barbosa, Fabiola Brasil and Brenol, Claiton Viegas and Xavier, Ricardo Machado and Chies, Jos{\'e} Artur Bogo and Veit, Tiago Degani} } @article {10514, title = {Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations.}, journal = {Nat Commun}, volume = {8}, year = {2017}, month = {2017 06 23}, pages = {15927}, abstract = {

The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully. We demonstrate relaxation of purifying selection in the isolates, leading to enrichment of rare and low-frequency functional variants, using novel statistics, DVxy and SVxy. We also develop an isolation-index (Isx) that predicts the overall level of such key genetic characteristics and can thus help guide population choice in future complex-trait association studies.

}, keywords = {European Continental Ancestry Group, Gene Frequency, Genetic Variation, Genetics, Population, Genome, Human, Humans, Polymorphism, Single Nucleotide, Whole Genome Sequencing}, issn = {2041-1723}, doi = {10.1038/ncomms15927}, author = {Xue, Yali and Mezzavilla, Massimo and Haber, Marc and McCarthy, Shane and Chen, Yuan and Narasimhan, Vagheesh and Gilly, Arthur and Ayub, Qasim and Colonna, Vincenza and Southam, Lorraine and Finan, Christopher and Massaia, Andrea and Chheda, Himanshu and Palta, Priit and Ritchie, Graham and Asimit, Jennifer and Dedoussis, George and Gasparini, Paolo and Palotie, Aarno and Ripatti, Samuli and Soranzo, Nicole and Toniolo, Daniela and Wilson, James F and Durbin, Richard and Tyler-Smith, Chris and Zeggini, Eleftheria} } @article {10538, title = {Training in Occupational Medicine: Jurisprudential Malfunctions in the Italian System and European Perspectives.}, journal = {Ann Ig}, volume = {29}, year = {2017}, month = {2017 May-Jun}, pages = {197-205}, abstract = {

BACKGROUND: To practice occupational health in Europe, a medical doctor must qualify in occupational medicine. This requires a period of postgraduate specialist medical training lasting a minimum of four years, in conformity with European regulations, to obtain a certificate of completion of training which is then mutually recognized within the entire European Union.

DISCUSSION: In 2002 an Italian law allowed doctors specialized in public health medicine and legal/forensic medicine to also practice as consultants in occupational medicine in the country. However a subsequent law in 2008 determined that only physicians specialized in occupational medicine could freely practice as consultants in this discipline. The other two categories (consultants in public health medicine and consultants in legal/forensic medicine) were required to undertake additional training (a Master course) to qualify as consultants in occupational medicine.

CONCLUSIONS: Doctors who entered postgraduate training in public health or legal/forensic medicine before 2008, with the option to practice also as consultants in occupational medicine upon completion of their training, suffered an unprecedented and legally questionable retroactive application of this new law which stripped them of previously acquired rights. Moreover, even after qualifying by undertaking this extra training in occupational medicine, the latter two categories of doctors do not have their training recognized in other member states of the European Union. To disallow the rights of doctors qualified in occupational medicine to work as consultants in the latter medical discipline elsewhere within the European Union seems a clear violation of professional rights and, as such, legal action could be taken to submit this issue to European attention.

}, keywords = {Certification, European Union, Italy, Occupational Medicine}, issn = {1120-9135}, doi = {10.7416/ai.2017.2147}, author = {Cegolon, L and Heymann, W C and Xodo, C and Lange, J H} } @article {10557, title = {Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.}, journal = {Am J Hum Genet}, volume = {100}, year = {2017}, month = {2017 Jun 01}, pages = {865-884}, abstract = {

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71\% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.

}, keywords = {Anthropometry, Body Height, Cohort Studies, Databases, Genetic, DNA Methylation, Female, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Lipodystrophy, Male, Meta-Analysis as Topic, Obesity, Physical Chromosome Mapping, Quantitative Trait Loci, Sequence Analysis, DNA, Sex Characteristics, Syndrome, United Kingdom}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2017.04.014}, author = {Tachmazidou, Ioanna and S{\"u}veges, D{\'a}niel and Min, Josine L and Ritchie, Graham R S and Steinberg, Julia and Walter, Klaudia and Iotchkova, Valentina and Schwartzentruber, Jeremy and Huang, Jie and Memari, Yasin and McCarthy, Shane and Crawford, Andrew A and Bombieri, Cristina and Cocca, Massimiliano and Farmaki, Aliki-Eleni and Gaunt, Tom R and Jousilahti, Pekka and Kooijman, Marjolein N and Lehne, Benjamin and Malerba, Giovanni and M{\"a}nnist{\"o}, Satu and Matchan, Angela and Medina-Gomez, Carolina and Metrustry, Sarah J and Nag, Abhishek and Ntalla, Ioanna and Paternoster, Lavinia and Rayner, Nigel W and Sala, Cinzia and Scott, William R and Shihab, Hashem A and Southam, Lorraine and St Pourcain, Beate and Traglia, Michela and Trajanoska, Katerina and Zaza, Gialuigi and Zhang, Weihua and Artigas, Mar{\'\i}a S and Bansal, Narinder and Benn, Marianne and Chen, Zhongsheng and Danecek, Petr and Lin, Wei-Yu and Locke, Adam and Luan, Jian{\textquoteright}an and Manning, Alisa K and Mulas, Antonella and Sidore, Carlo and Tybjaerg-Hansen, Anne and Varbo, Anette and Zoledziewska, Magdalena and Finan, Chris and Hatzikotoulas, Konstantinos and Hendricks, Audrey E and Kemp, John P and Moayyeri, Alireza and Panoutsopoulou, Kalliope and Szpak, Michal and Wilson, Scott G and Boehnke, Michael and Cucca, Francesco and Di Angelantonio, Emanuele and Langenberg, Claudia and Lindgren, Cecilia and McCarthy, Mark I and Morris, Andrew P and Nordestgaard, B{\o}rge G and Scott, Robert A and Tobin, Martin D and Wareham, Nicholas J and Burton, Paul and Chambers, John C and Smith, George Davey and Dedoussis, George and Felix, Janine F and Franco, Oscar H and Gambaro, Giovanni and Gasparini, Paolo and Hammond, Christopher J and Hofman, Albert and Jaddoe, Vincent W V and Kleber, Marcus and Kooner, Jaspal S and Perola, Markus and Relton, Caroline and Ring, Susan M and Rivadeneira, Fernando and Salomaa, Veikko and Spector, Timothy D and Stegle, Oliver and Toniolo, Daniela and Uitterlinden, Andr{\'e} G and Barroso, In{\^e}s and Greenwood, Celia M T and Perry, John R B and Walker, Brian R and Butterworth, Adam S and Xue, Yali and Durbin, Richard and Small, Kerrin S and Soranzo, Nicole and Timpson, Nicholas J and Zeggini, Eleftheria} } @article {8057, title = {Ficolin Gene Polymorphisms in Systemic Lupus Erythematosus and Rheumatoid Arthritis.}, journal = {Ann Hum Genet}, year = {2015}, month = {2015 Oct 14}, abstract = {

Systemic lupus erythemathosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases characterized by an immune balance breakdown and by chronic inflammation. Several findings link SLE and RA development with the complement system and ficolin components have emerged as candidates for disease development. Since genetic association studies with ficolin genes in SLE and RA have not yet been conducted in a Brazilian population, the aim of this study was to determine whether polymorphisms of ficolin-1(FCN1) and ficolin-2 (FCN2) genes are associated with SLE and RA susceptibility as well as disease manifestation. Two SNPs within FCN1 (rs2989727 and 1071583) and three in FCN2 (rs17514136, rs3124954, and rs7851696) were studied in 208 SLE and184 RA patients as well as 264 healthy individuals in a Southeast Brazilian population. For SLE patients, the FCN2 rs17514136 SNP was associated with a more severe disease (SLICC) (p = 0.0067). Furthermore, an association between the occurrence of nephritis and the T/T genotype for FCN2 rs3124954 SNP (p = 0.047, OR = 3.17, 95\%CI = 1.34-7.5) was observed. No association was observed between the studied polymorphisms and RA development. Thus, our data support involvement of the FCN2 gene in the SLE phenotype.

}, issn = {1469-1809}, doi = {10.1111/ahg.12129}, author = {Addobbati, Catarina and De Azev{\^e}do Silva, Jaqueline and A C Tavares, Nath{\'a}lia and Monticielo, Odirlei and M Xavier, Ricardo and T Brenol, Jo{\~a}o Carlos and Crovella, Sergio and B Chies, Jos{\'e} Artur and Sandrin-Garcia, Paula} } @article {8069, title = {Genetic evidence for an origin of the Armenians from Bronze Age mixing of multiple populations.}, journal = {Eur J Hum Genet}, year = {2015}, month = {2015 Oct 21}, abstract = {

The Armenians are a culturally isolated population who historically inhabited a region in the Near East bounded by the Mediterranean and Black seas and the Caucasus, but remain under-represented in genetic studies and have a complex history including a major geographic displacement during World War I. Here, we analyse genome-wide variation in 173 Armenians and compare them with 78 other worldwide populations. We find that Armenians form a distinctive cluster linking the Near East, Europe, and the Caucasus. We show that Armenian diversity can be explained by several mixtures of Eurasian populations that occurred between ~3000 and ~2000 bce, a period characterized by major population migrations after the domestication of the horse, appearance of chariots, and the rise of advanced civilizations in the Near East. However, genetic signals of population mixture cease after ~1200 bce when Bronze Age civilizations in the Eastern Mediterranean world suddenly and violently collapsed. Armenians have since remained isolated and genetic structure within the population developed ~500 years ago when Armenia was divided between the Ottomans and the Safavid Empire in Iran. Finally, we show that Armenians have higher genetic affinity to Neolithic Europeans than other present-day Near Easterners, and that 29\% of Armenian ancestry may originate from an ancestral population that is best represented by Neolithic Europeans.European Journal of Human Genetics advance online publication, 21 October 2015; doi:10.1038/ejhg.2015.206.

}, issn = {1476-5438}, doi = {10.1038/ejhg.2015.206}, author = {Haber, Marc and Mezzavilla, Massimo and Xue, Yali and Comas, David and Gasparini, Paolo and Zalloua, Pierre and Tyler-Smith, Chris} } @article {7700, title = {Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.}, journal = {Nat Genet}, volume = {47}, year = {2015}, month = {2015 May}, pages = {535-8}, abstract = {

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.

}, keywords = {Adult, Child, Preschool, DNA Mutational Analysis, Erythrocytes, Abnormal, Exome, Female, Genetic Association Studies, Genetic Predisposition to Disease, Germ-Line Mutation, HEK293 Cells, Hematologic Diseases, Humans, Male, Mutation, Missense, Pedigree, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-ets, Repressor Proteins, Thrombocytopenia}, issn = {1546-1718}, doi = {10.1038/ng.3253}, author = {Noetzli, Leila and Lo, Richard W and Lee-Sherick, Alisa B and Callaghan, Michael and Noris, Patrizia and Savoia, Anna and Rajpurkar, Madhvi and Jones, Kenneth and Gowan, Katherine and Balduini, Carlo L and Pecci, Alessandro and Gnan, Chiara and De Rocco, Daniela and Doubek, Michael and Li, Ling and Lu, Lily and Leung, Richard and Landolt-Marticorena, Carolina and Hunger, Stephen and Heller, Paula and Gutierrez-Hartmann, Arthur and Xiayuan, Liang and Pluthero, Fred G and Rowley, Jesse W and Weyrich, Andrew S and Kahr, Walter H A and Porter, Christopher C and Di Paola, Jorge} } @article {8043, title = {Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.}, journal = {Lancet}, volume = {386}, year = {2015}, month = {2015 Dec 5}, pages = {2287-323}, abstract = {

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.

FINDINGS: All risks combined account for 57{\textperiodcentered}2\% (95\% uncertainty interval [UI] 55{\textperiodcentered}8-58{\textperiodcentered}5) of deaths and 41{\textperiodcentered}6\% (40{\textperiodcentered}1-43{\textperiodcentered}0) of DALYs. Risks quantified account for 87{\textperiodcentered}9\% (86{\textperiodcentered}5-89{\textperiodcentered}3) of cardiovascular disease DALYs, ranging to a low of 0\% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5\% of DALYs: dietary risks accounting for 11{\textperiodcentered}3 million deaths and 241{\textperiodcentered}4 million DALYs, high systolic blood pressure for 10{\textperiodcentered}4 million deaths and 208{\textperiodcentered}1 million DALYs, child and maternal malnutrition for 1{\textperiodcentered}7 million deaths and 176{\textperiodcentered}9 million DALYs, tobacco smoke for 6{\textperiodcentered}1 million deaths and 143{\textperiodcentered}5 million DALYs, air pollution for 5{\textperiodcentered}5 million deaths and 141{\textperiodcentered}5 million DALYs, and high BMI for 4{\textperiodcentered}4 million deaths and 134{\textperiodcentered}0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.

INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

FUNDING: Bill \& Melinda Gates Foundation.

}, issn = {1474-547X}, doi = {10.1016/S0140-6736(15)00128-2}, author = {Forouzanfar, Mohammad H and Alexander, Lily and Anderson, H Ross and Bachman, Victoria F and Biryukov, Stan and Brauer, Michael and Burnett, Richard and Casey, Daniel and Coates, Matthew M and Cohen, Aaron and Delwiche, Kristen and Estep, Kara and Frostad, Joseph J and Astha, K C and Kyu, Hmwe H and Moradi-Lakeh, Maziar and Ng, Marie and Slepak, Erica Leigh and Thomas, Bernadette A and Wagner, Joseph and Aasvang, Gunn Marit and Abbafati, Cristiana and Abbasoglu Ozgoren, Ayse and Abd-Allah, Foad and Abera, Semaw F and Aboyans, Victor and Abraham, Biju and Abraham, Jerry Puthenpurakal and Abubakar, Ibrahim and Abu-Rmeileh, Niveen M E and Aburto, Tania C and Achoki, Tom and Adelekan, Ademola and Adofo, Koranteng and Adou, Ars{\`e}ne K and Adsuar, Jos{\'e} C and Afshin, Ashkan and Agardh, Emilie E and Al Khabouri, Mazin J and Al Lami, Faris H and Alam, Sayed Saidul and Alasfoor, Deena and Albittar, Mohammed I and Alegretti, Miguel A and Aleman, Alicia V and Alemu, Zewdie A and Alfonso-Cristancho, Rafael and Alhabib, Samia and Ali, Raghib and Ali, Mohammed K and Alla, Fran{\c c}ois and Allebeck, Peter and Allen, Peter J and Alsharif, Ubai and Alvarez, Elena and Alvis-Guzm{\'a}n, Nelson and Amankwaa, Adansi A and Amare, Azmeraw T and Ameh, Emmanuel A and Ameli, Omid and Amini, Heresh and Ammar, Walid and Anderson, Benjamin O and Antonio, Carl Abelardo T and Anwari, Palwasha and Argeseanu Cunningham, Solveig and Arnl{\"o}v, Johan and Arsenijevic, Valentina S Arsic and Artaman, Al and Asghar, Rana J and Assadi, Reza and Atkins, Lydia S and Atkinson, Charles and Avila, Marco A and Awuah, Baffour and Badawi, Alaa and Bahit, Maria C and Bakfalouni, Talal and Balakrishnan, Kalpana and Balalla, Shivanthi and Balu, Ravi Kumar and Banerjee, Amitava and Barber, Ryan M and Barker-Collo, Suzanne L and Barquera, Simon and Barregard, Lars and Barrero, Lope H and Barrientos-Gutierrez, Tonatiuh and Basto-Abreu, Ana C and Basu, Arindam and Basu, Sanjay and Basulaiman, Mohammed O and Batis Ruvalcaba, Carolina and Beardsley, Justin and Bedi, Neeraj and Bekele, Tolesa and Bell, Michelle L and Benjet, Corina and Bennett, Derrick A and Benzian, Habib and Bernabe, Eduardo and Beyene, Tariku J and Bhala, Neeraj and Bhalla, Ashish and Bhutta, Zulfiqar A and Bikbov, Boris and Bin Abdulhak, Aref A and Blore, Jed D and Blyth, Fiona M and Bohensky, Megan A and Bora Ba{\c s}ara, Berrak and Borges, Guilherme and Bornstein, Natan M and Bose, Dipan and Boufous, Soufiane and Bourne, Rupert R and Brainin, Michael and Brazinova, Alexandra and Breitborde, Nicholas J and Brenner, Hermann and Briggs, Adam D M and Broday, David M and Brooks, Peter M and Bruce, Nigel G and Brugha, Traolach S and Brunekreef, Bert and Buchbinder, Rachelle and Bui, Linh N and Bukhman, Gene and Bulloch, Andrew G and Burch, Michael and Burney, Peter G J and Campos-Nonato, Ismael R and Campuzano, Julio C and Cantoral, Alejandra J and Caravanos, Jack and C{\'a}rdenas, Rosario and Cardis, Elisabeth and Carpenter, David O and Caso, Valeria and Casta{\~n}eda-Orjuela, Carlos A and Castro, Ruben E and Catal{\'a}-L{\'o}pez, Ferr{\'a}n and Cavalleri, Fiorella and Cavlin, Alanur and Chadha, Vineet K and Chang, Jung-Chen and Charlson, Fiona J and Chen, Honglei and Chen, Wanqing and Chen, Zhengming and Chiang, Peggy P and Chimed-Ochir, Odgerel and Chowdhury, Rajiv and Christophi, Costas A and Chuang, Ting-Wu and Chugh, Sumeet S and Cirillo, Massimo and Cla{\ss}en, Thomas K D and Colistro, Valentina and Colomar, Mercedes and Colquhoun, Samantha M and Contreras, Alejandra G and Cooper, Cyrus and Cooperrider, Kimberly and Cooper, Leslie T and Coresh, Josef and Courville, Karen J and Criqui, Michael H and Cuevas-Nasu, Lucia and Damsere-Derry, James and Danawi, Hadi and Dandona, Lalit and Dandona, Rakhi and Dargan, Paul I and Davis, Adrian and Davitoiu, Dragos V and Dayama, Anand and de Castro, E Filipa and De la Cruz-G{\'o}ngora, Vanessa and De Leo, Diego and de Lima, Gra{\c c}a and Degenhardt, Louisa and del Pozo-Cruz, Borja and Dellavalle, Robert P and Deribe, Kebede and Derrett, Sarah and Des Jarlais, Don C and Dessalegn, Muluken and deVeber, Gabrielle A and Devries, Karen M and Dharmaratne, Samath D and Dherani, Mukesh K and Dicker, Daniel and Ding, Eric L and Dokova, Klara and Dorsey, E Ray and Driscoll, Tim R and Duan, Leilei and Durrani, Adnan M and Ebel, Beth E and Ellenbogen, Richard G and Elshrek, Yousef M and Endres, Matthias and Ermakov, Sergey P and Erskine, Holly E and Eshrati, Babak and Esteghamati, Alireza and Fahimi, Saman and Faraon, Emerito Jose A and Farzadfar, Farshad and Fay, Derek F J and Feigin, Valery L and Feigl, Andrea B and Fereshtehnejad, Seyed-Mohammad and Ferrari, Alize J and Ferri, Cleusa P and Flaxman, Abraham D and Fleming, Thomas D and Foigt, Nataliya and Foreman, Kyle J and Paleo, Urbano Fra and Franklin, Richard C and Gabbe, Belinda and Gaffikin, Lynne and Gakidou, Emmanuela and Gamkrelidze, Amiran and Gankp{\'e}, Fortun{\'e} G and Gansevoort, Ron T and Garc{\'\i}a-Guerra, Francisco A and Gasana, Evariste and Geleijnse, Johanna M and Gessner, Bradford D and Gething, Pete and Gibney, Katherine B and Gillum, Richard F and Ginawi, Ibrahim A M and Giroud, Maurice and Giussani, Giorgia and Goenka, Shifalika and Goginashvili, Ketevan and Gomez Dantes, Hector and Gona, Philimon and Gonzalez de Cosio, Teresita and Gonz{\'a}lez-Castell, Dinorah and Gotay, Carolyn C and Goto, Atsushi and Gouda, Hebe N and Guerrant, Richard L and Gugnani, Harish C and Guillemin, Francis and Gunnell, David and Gupta, Rahul and Gupta, Rajeev and Guti{\'e}rrez, Reyna A and Hafezi-Nejad, Nima and Hagan, Holly and Hagstromer, Maria and Halasa, Yara A and Hamadeh, Randah R and Hammami, Mouhanad and Hankey, Graeme J and Hao, Yuantao and Harb, Hilda L and Haregu, Tilahun Nigatu and Haro, Josep Maria and Havmoeller, Rasmus and Hay, Simon I and Hedayati, Mohammad T and Heredia-Pi, Ileana B and Hernandez, Lucia and Heuton, Kyle R and Heydarpour, Pouria and Hijar, Martha and Hoek, Hans W and Hoffman, Howard J and Hornberger, John C and Hosgood, H Dean and Hoy, Damian G and Hsairi, Mohamed and Hu, Guoqing and Hu, Howard and Huang, Cheng and Huang, John J and Hubbell, Bryan J and Huiart, Laetitia and Husseini, Abdullatif and Iannarone, Marissa L and Iburg, Kim M and Idrisov, Bulat T and Ikeda, Nayu and Innos, Kaire and Inoue, Manami and Islami, Farhad and Ismayilova, Samaya and Jacobsen, Kathryn H and Jansen, Henrica A and Jarvis, Deborah L and Jassal, Simerjot K and Jauregui, Alejandra and Jayaraman, Sudha and Jeemon, Panniyammakal and Jensen, Paul N and Jha, Vivekanand and Jiang, Fan and Jiang, Guohong and Jiang, Ying and Jonas, Jost B and Juel, Knud and Kan, Haidong and Kany Roseline, Sidibe S and Karam, Nadim E and Karch, Andr{\'e} and Karema, Corine K and Karthikeyan, Ganesan and Kaul, Anil and Kawakami, Norito and Kazi, Dhruv S and Kemp, Andrew H and Kengne, Andre P and Keren, Andre and Khader, Yousef S and Khalifa, Shams Eldin Ali Hassan and Khan, Ejaz A and Khang, Young-Ho and Khatibzadeh, Shahab and Khonelidze, Irma and Kieling, Christian and Kim, Daniel and Kim, Sungroul and Kim, Yunjin and Kimokoti, Ruth W and Kinfu, Yohannes and Kinge, Jonas M and Kissela, Brett M and Kivipelto, Miia and Knibbs, Luke D and Knudsen, Ann Kristin and Kokubo, Yoshihiro and Kose, M Rifat and Kosen, Soewarta and Kraemer, Alexander and Kravchenko, Michael and Krishnaswami, Sanjay and Kromhout, Hans and Ku, Tiffany and Kuate Defo, Barthelemy and Kucuk Bicer, Burcu and Kuipers, Ernst J and Kulkarni, Chanda and Kulkarni, Veena S and Kumar, G Anil and Kwan, Gene F and Lai, Taavi and Lakshmana Balaji, Arjun and Lalloo, Ratilal and Lallukka, Tea and Lam, Hilton and Lan, Qing and Lansingh, Van C and Larson, Heidi J and Larsson, Anders and Laryea, Dennis O and Lavados, Pablo M and Lawrynowicz, Alicia E and Leasher, Janet L and Lee, Jong-Tae and Leigh, James and Leung, Ricky and Levi, Miriam and Li, Yichong and Li, Yongmei and Liang, Juan and Liang, Xiaofeng and Lim, Stephen S and Lindsay, M Patrice and Lipshultz, Steven E and Liu, Shiwei and Liu, Yang and Lloyd, Belinda K and Logroscino, Giancarlo and London, Stephanie J and Lopez, Nancy and Lortet-Tieulent, Joannie and Lotufo, Paulo A and Lozano, Rafael and Lunevicius, Raimundas and Ma, Jixiang and Ma, Stefan and Machado, Vasco M P and MacIntyre, Michael F and Magis-Rodriguez, Carlos and Mahdi, Abbas A and Majdan, Marek and Malekzadeh, Reza and Mangalam, Srikanth and Mapoma, Christopher C and Marape, Marape and Marcenes, Wagner and Margolis, David J and Margono, Christopher and Marks, Guy B and Martin, Randall V and Marzan, Melvin B and Mashal, Mohammad T and Masiye, Felix and Mason-Jones, Amanda J and Matsushita, Kunihiro and Matzopoulos, Richard and Mayosi, Bongani M and Mazorodze, Tasara T and McKay, Abigail C and McKee, Martin and McLain, Abigail and Meaney, Peter A and Medina, Catalina and Mehndiratta, Man Mohan and Mejia-Rodriguez, Fabiola and Mekonnen, Wubegzier and Melaku, Yohannes A and Meltzer, Michele and Memish, Ziad A and Mendoza, Walter and Mensah, George A and Meretoja, Atte and Mhimbira, Francis Apolinary and Micha, Renata and Miller, Ted R and Mills, Edward J and Misganaw, Awoke and Mishra, Santosh and Mohamed Ibrahim, Norlinah and Mohammad, Karzan A and Mokdad, Ali H and Mola, Glen L and Monasta, Lorenzo and Monta{\~n}ez Hernandez, Julio C and Montico, Marcella and Moore, Ami R and Morawska, Lidia and Mori, Rintaro and Moschandreas, Joanna and Moturi, Wilkister N and Mozaffarian, Dariush and Mueller, Ulrich O and Mukaigawara, Mitsuru and Mullany, Erin C and Murthy, Kinnari S and Naghavi, Mohsen and Nahas, Ziad and Naheed, Aliya and Naidoo, Kovin S and Naldi, Luigi and Nand, Devina and Nangia, Vinay and Narayan, K M Venkat and Nash, Denis and Neal, Bruce and Nejjari, Chakib and Neupane, Sudan P and Newton, Charles R and Ngalesoni, Frida N and Ngirabega, Jean de Dieu and Nguyen, Grant and Nguyen, Nhung T and Nieuwenhuijsen, Mark J and Nisar, Muhammad I and Nogueira, Jos{\'e} R and Nolla, Joan M and Nolte, Sandra and Norheim, Ole F and Norman, Rosana E and Norrving, Bo and Nyakarahuka, Luke and Oh, In-Hwan and Ohkubo, Takayoshi and Olusanya, Bolajoko O and Omer, Saad B and Opio, John Nelson and Orozco, Ricardo and Pagcatipunan, Rodolfo S and Pain, Amanda W and Pandian, Jeyaraj D and Panelo, Carlo Irwin A and Papachristou, Christina and Park, Eun-Kee and Parry, Charles D and Paternina Caicedo, Angel J and Patten, Scott B and Paul, Vinod K and Pavlin, Boris I and Pearce, Neil and Pedraza, Lilia S and Pedroza, Andrea and Pejin Stokic, Ljiljana and Pekericli, Ayfer and Pereira, David M and Perez-Padilla, Rogelio and Perez-Ruiz, Fernando and Perico, Norberto and Perry, Samuel A L and Pervaiz, Aslam and Pesudovs, Konrad and Peterson, Carrie B and Petzold, Max and Phillips, Michael R and Phua, Hwee Pin and Plass, Dietrich and Poenaru, Dan and Polanczyk, Guilherme V and Polinder, Suzanne and Pond, Constance D and Pope, C Arden and Pope, Daniel and Popova, Svetlana and Pourmalek, Farshad and Powles, John and Prabhakaran, Dorairaj and Prasad, Noela M and Qato, Dima M and Quezada, Amado D and Quistberg, D Alex A and Racap{\'e}, Lionel and Rafay, Anwar and Rahimi, Kazem and Rahimi-Movaghar, Vafa and Rahman, Sajjad Ur and Raju, Murugesan and Rakovac, Ivo and Rana, Saleem M and Rao, Mayuree and Razavi, Homie and Reddy, K Srinath and Refaat, Amany H and Rehm, J{\"u}rgen and Remuzzi, Giuseppe and Ribeiro, Antonio L and Riccio, Patricia M and Richardson, Lee and Riederer, Anne and Robinson, Margaret and Roca, Anna and Rodriguez, Alina and Rojas-Rueda, David and Romieu, Isabelle and Ronfani, Luca and Room, Robin and Roy, Nobhojit and Ruhago, George M and Rushton, Lesley and Sabin, Nsanzimana and Sacco, Ralph L and Saha, Sukanta and Sahathevan, Ramesh and Sahraian, Mohammad Ali and Salomon, Joshua A and Salvo, Deborah and Sampson, Uchechukwu K and Sanabria, Juan R and Sanchez, Luz Maria and S{\'a}nchez-Pimienta, Tania G and Sanchez-Riera, Lidia and Sandar, Logan and Santos, Itamar S and Sapkota, Amir and Satpathy, Maheswar and Saunders, James E and Sawhney, Monika and Saylan, Mete I and Scarborough, Peter and Schmidt, J{\"u}rgen C and Schneider, Ione J C and Sch{\"o}ttker, Ben and Schwebel, David C and Scott, James G and Seedat, Soraya and Sepanlou, Sadaf G and Serdar, Berrin and Servan-Mori, Edson E and Shaddick, Gavin and Shahraz, Saeid and Levy, Teresa Shamah and Shangguan, Siyi and She, Jun and Sheikhbahaei, Sara and Shibuya, Kenji and Shin, Hwashin H and Shinohara, Yukito and Shiri, Rahman and Shishani, Kawkab and Shiue, Ivy and Sigfusdottir, Inga D and Silberberg, Donald H and Simard, Edgar P and Sindi, Shireen and Singh, Abhishek and Singh, Gitanjali M and Singh, Jasvinder A and Skirbekk, Vegard and Sliwa, Karen and Soljak, Michael and Soneji, Samir and S{\o}reide, Kjetil and Soshnikov, Sergey and Sposato, Luciano A and Sreeramareddy, Chandrashekhar T and Stapelberg, Nicolas J C and Stathopoulou, Vasiliki and Steckling, Nadine and Stein, Dan J and Stein, Murray B and Stephens, Natalie and St{\"o}ckl, Heidi and Straif, Kurt and Stroumpoulis, Konstantinos and Sturua, Lela and Sunguya, Bruno F and Swaminathan, Soumya and Swaroop, Mamta and Sykes, Bryan L and Tabb, Karen M and Takahashi, Ken and Talongwa, Roberto T and Tandon, Nikhil and Tanne, David and Tanner, Marcel and Tavakkoli, Mohammad and Te Ao, Braden J and Teixeira, Carolina M and T{\'e}llez Rojo, Martha M and Terkawi, Abdullah S and Texcalac-Sangrador, Jos{\'e} Luis and Thackway, Sarah V and Thomson, Blake and Thorne-Lyman, Andrew L and Thrift, Amanda G and Thurston, George D and Tillmann, Taavi and Tobollik, Myriam and Tonelli, Marcello and Topouzis, Fotis and Towbin, Jeffrey A and Toyoshima, Hideaki and Traebert, Jefferson and Tran, Bach X and Trasande, Leonardo and Trillini, Matias and Trujillo, Ulises and Dimbuene, Zacharie Tsala and Tsilimbaris, Miltiadis and Tuzcu, Emin Murat and Uchendu, Uche S and Ukwaja, Kingsley N and Uzun, Selen B and van de Vijver, Steven and Van Dingenen, Rita and van Gool, Coen H and van Os, Jim and Varakin, Yuri Y and Vasankari, Tommi J and Vasconcelos, Ana Maria N and Vavilala, Monica S and Veerman, Lennert J and Velasquez-Melendez, Gustavo and Venketasubramanian, N and Vijayakumar, Lakshmi and Villalpando, Salvador and Violante, Francesco S and Vlassov, Vasiliy Victorovich and Vollset, Stein Emil and Wagner, Gregory R and Waller, Stephen G and Wallin, Mitchell T and Wan, Xia and Wang, Haidong and Wang, JianLi and Wang, Linhong and Wang, Wenzhi and Wang, Yanping and Warouw, Tati S and Watts, Charlotte H and Weichenthal, Scott and Weiderpass, Elisabete and Weintraub, Robert G and Werdecker, Andrea and Wessells, K Ryan and Westerman, Ronny and Whiteford, Harvey A and Wilkinson, James D and Williams, Hywel C and Williams, Thomas N and Woldeyohannes, Solomon M and Wolfe, Charles D A and Wong, John Q and Woolf, Anthony D and Wright, Jonathan L and Wurtz, Brittany and Xu, Gelin and Yan, Lijing L and Yang, Gonghuan and Yano, Yuichiro and Ye, Pengpeng and Yenesew, Muluken and Yent{\"u}r, G{\"o}kalp K and Yip, Paul and Yonemoto, Naohiro and Yoon, Seok-Jun and Younis, Mustafa Z and Younoussi, Zourkaleini and Yu, Chuanhua and Zaki, Maysaa E and Zhao, Yong and Zheng, Yingfeng and Zhou, Maigeng and Zhu, Jun and Zhu, Shankuan and Zou, Xiaonong and Zunt, Joseph R and Lopez, Alan D and Vos, Theo and Murray, Christopher J} } @article {8044, title = {Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition.}, journal = {Lancet}, volume = {386}, year = {2015}, month = {2015 Nov 28}, pages = {2145-91}, abstract = {

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95\% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95\% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6{\textperiodcentered}2 years (95\% UI 5{\textperiodcentered}6-6{\textperiodcentered}6), from 65{\textperiodcentered}3 years (65{\textperiodcentered}0-65{\textperiodcentered}6) in 1990 to 71{\textperiodcentered}5 years (71{\textperiodcentered}0-71{\textperiodcentered}9) in 2013, HALE at birth rose by 5{\textperiodcentered}4 years (4{\textperiodcentered}9-5{\textperiodcentered}8), from 56{\textperiodcentered}9 years (54{\textperiodcentered}5-59{\textperiodcentered}1) to 62{\textperiodcentered}3 years (59{\textperiodcentered}7-64{\textperiodcentered}8), total DALYs fell by 3{\textperiodcentered}6\% (0{\textperiodcentered}3-7{\textperiodcentered}4), and age-standardised DALY rates per 100 000 people fell by 26{\textperiodcentered}7\% (24{\textperiodcentered}6-29{\textperiodcentered}1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50\% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10\% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

FUNDING: Bill \& Melinda Gates Foundation.

}, keywords = {Aged, Chronic Disease, Communicable Diseases, Female, Global Health, Health Transition, Humans, Life Expectancy, Male, Middle Aged, Mortality, Premature, Quality-Adjusted Life Years, Socioeconomic Factors, Wounds and Injuries}, issn = {1474-547X}, doi = {10.1016/S0140-6736(15)61340-X}, author = {Murray, Christopher J L and Barber, Ryan M and Foreman, Kyle J and Abbasoglu Ozgoren, Ayse and Abd-Allah, Foad and Abera, Semaw F and Aboyans, Victor and Abraham, Jerry P and Abubakar, Ibrahim and Abu-Raddad, Laith J and Abu-Rmeileh, Niveen M and Achoki, Tom and Ackerman, Ilana N and Ademi, Zanfina and Adou, Ars{\`e}ne K and Adsuar, Jos{\'e} C and Afshin, Ashkan and Agardh, Emilie E and Alam, Sayed Saidul and Alasfoor, Deena and Albittar, Mohammed I and Alegretti, Miguel A and Alemu, Zewdie A and Alfonso-Cristancho, Rafael and Alhabib, Samia and Ali, Raghib and Alla, Fran{\c c}ois and Allebeck, Peter and AlMazroa, Mohammad A and Alsharif, Ubai and Alvarez, Elena and Alvis-Guzm{\'a}n, Nelson and Amare, Azmeraw T and Ameh, Emmanuel A and Amini, Heresh and Ammar, Walid and Anderson, H Ross and Anderson, Benjamin O and Antonio, Carl Abelardo T and Anwari, Palwasha and Arnl{\"o}v, Johan and Arsic Arsenijevic, Valentina S and Artaman, Al and Asghar, Rana J and Assadi, Reza and Atkins, Lydia S and Avila, Marco A and Awuah, Baffour and Bachman, Victoria F and Badawi, Alaa and Bahit, Maria C and Balakrishnan, Kalpana and Banerjee, Amitava and Barker-Collo, Suzanne L and Barquera, Simon and Barregard, Lars and Barrero, Lope H and Basu, Arindam and Basu, Sanjay and Basulaiman, Mohammed O and Beardsley, Justin and Bedi, Neeraj and Beghi, Ettore and Bekele, Tolesa and Bell, Michelle L and Benjet, Corina and Bennett, Derrick A and Bensenor, Isabela M and Benzian, Habib and Bernabe, Eduardo and Bertozzi-Villa, Amelia and Beyene, Tariku J and Bhala, Neeraj and Bhalla, Ashish and Bhutta, Zulfiqar A and Bienhoff, Kelly and Bikbov, Boris and Biryukov, Stan and Blore, Jed D and Blosser, Christopher D and Blyth, Fiona M and Bohensky, Megan A and Bolliger, Ian W and Bora Ba{\c s}ara, Berrak and Bornstein, Natan M and Bose, Dipan and Boufous, Soufiane and Bourne, Rupert R A and Boyers, Lindsay N and Brainin, Michael and Brayne, Carol E and Brazinova, Alexandra and Breitborde, Nicholas J K and Brenner, Hermann and Briggs, Adam D and Brooks, Peter M and Brown, Jonathan C and Brugha, Traolach S and Buchbinder, Rachelle and Buckle, Geoffrey C and Budke, Christine M and Bulchis, Anne and Bulloch, Andrew G and Campos-Nonato, Ismael R and Carabin, H{\'e}l{\`e}ne and Carapetis, Jonathan R and C{\'a}rdenas, Rosario and Carpenter, David O and Caso, Valeria and Casta{\~n}eda-Orjuela, Carlos A and Castro, Ruben E and Catal{\'a}-L{\'o}pez, Ferr{\'a}n and Cavalleri, Fiorella and Cavlin, Alanur and Chadha, Vineet K and Chang, Jung-Chen and Charlson, Fiona J and Chen, Honglei and Chen, Wanqing and Chiang, Peggy P and Chimed-Ochir, Odgerel and Chowdhury, Rajiv and Christensen, Hanne and Christophi, Costas A and Cirillo, Massimo and Coates, Matthew M and Coffeng, Luc E and Coggeshall, Megan S and Colistro, Valentina and Colquhoun, Samantha M and Cooke, Graham S and Cooper, Cyrus and Cooper, Leslie T and Coppola, Luis M and Cortinovis, Monica and Criqui, Michael H and Crump, John A and Cuevas-Nasu, Lucia and Danawi, Hadi and Dandona, Lalit and Dandona, Rakhi and Dansereau, Emily and Dargan, Paul I and Davey, Gail and Davis, Adrian and Davitoiu, Dragos V and Dayama, Anand and De Leo, Diego and Degenhardt, Louisa and del Pozo-Cruz, Borja and Dellavalle, Robert P and Deribe, Kebede and Derrett, Sarah and Des Jarlais, Don C and Dessalegn, Muluken and Dharmaratne, Samath D and Dherani, Mukesh K and Diaz-Torn{\'e}, Cesar and Dicker, Daniel and Ding, Eric L and Dokova, Klara and Dorsey, E Ray and Driscoll, Tim R and Duan, Leilei and Duber, Herbert C and Ebel, Beth E and Edmond, Karen M and Elshrek, Yousef M and Endres, Matthias and Ermakov, Sergey P and Erskine, Holly E and Eshrati, Babak and Esteghamati, Alireza and Estep, Kara and Faraon, Emerito Jose A and Farzadfar, Farshad and Fay, Derek F and Feigin, Valery L and Felson, David T and Fereshtehnejad, Seyed-Mohammad and Fernandes, Jefferson G and Ferrari, Alize J and Fitzmaurice, Christina and Flaxman, Abraham D and Fleming, Thomas D and Foigt, Nataliya and Forouzanfar, Mohammad H and Fowkes, F Gerry R and Paleo, Urbano Fra and Franklin, Richard C and F{\"u}rst, Thomas and Gabbe, Belinda and Gaffikin, Lynne and Gankp{\'e}, Fortun{\'e} G and Geleijnse, Johanna M and Gessner, Bradford D and Gething, Peter and Gibney, Katherine B and Giroud, Maurice and Giussani, Giorgia and Gomez Dantes, Hector and Gona, Philimon and Gonzalez-Medina, Diego and Gosselin, Richard A and Gotay, Carolyn C and Goto, Atsushi and Gouda, Hebe N and Graetz, Nicholas and Gugnani, Harish C and Gupta, Rahul and Gupta, Rajeev and Guti{\'e}rrez, Reyna A and Haagsma, Juanita and Hafezi-Nejad, Nima and Hagan, Holly and Halasa, Yara A and Hamadeh, Randah R and Hamavid, Hannah and Hammami, Mouhanad and Hancock, Jamie and Hankey, Graeme J and Hansen, Gillian M and Hao, Yuantao and Harb, Hilda L and Haro, Josep Maria and Havmoeller, Rasmus and Hay, Simon I and Hay, Roderick J and Heredia-Pi, Ileana B and Heuton, Kyle R and Heydarpour, Pouria and Higashi, Hideki and Hijar, Martha and Hoek, Hans W and Hoffman, Howard J and Hosgood, H Dean and Hossain, Mazeda and Hotez, Peter J and Hoy, Damian G and Hsairi, Mohamed and Hu, Guoqing and Huang, Cheng and Huang, John J and Husseini, Abdullatif and Huynh, Chantal and Iannarone, Marissa L and Iburg, Kim M and Innos, Kaire and Inoue, Manami and Islami, Farhad and Jacobsen, Kathryn H and Jarvis, Deborah L and Jassal, Simerjot K and Jee, Sun Ha and Jeemon, Panniyammakal and Jensen, Paul N and Jha, Vivekanand and Jiang, Guohong and Jiang, Ying and Jonas, Jost B and Juel, Knud and Kan, Haidong and Karch, Andr{\'e} and Karema, Corine K and Karimkhani, Chante and Karthikeyan, Ganesan and Kassebaum, Nicholas J and Kaul, Anil and Kawakami, Norito and Kazanjan, Konstantin and Kemp, Andrew H and Kengne, Andre P and Keren, Andre and Khader, Yousef S and Khalifa, Shams Eldin A and Khan, Ejaz A and Khan, Gulfaraz and Khang, Young-Ho and Kieling, Christian and Kim, Daniel and Kim, Sungroul and Kim, Yunjin and Kinfu, Yohannes and Kinge, Jonas M and Kivipelto, Miia and Knibbs, Luke D and Knudsen, Ann Kristin and Kokubo, Yoshihiro and Kosen, Soewarta and Krishnaswami, Sanjay and Kuate Defo, Barthelemy and Kucuk Bicer, Burcu and Kuipers, Ernst J and Kulkarni, Chanda and Kulkarni, Veena S and Kumar, G Anil and Kyu, Hmwe H and Lai, Taavi and Lalloo, Ratilal and Lallukka, Tea and Lam, Hilton and Lan, Qing and Lansingh, Van C and Larsson, Anders and Lawrynowicz, Alicia E B and Leasher, Janet L and Leigh, James and Leung, Ricky and Levitz, Carly E and Li, Bin and Li, Yichong and Li, Yongmei and Lim, Stephen S and Lind, Maggie and Lipshultz, Steven E and Liu, Shiwei and Liu, Yang and Lloyd, Belinda K and Lofgren, Katherine T and Logroscino, Giancarlo and Looker, Katharine J and Lortet-Tieulent, Joannie and Lotufo, Paulo A and Lozano, Rafael and Lucas, Robyn M and Lunevicius, Raimundas and Lyons, Ronan A and Ma, Stefan and MacIntyre, Michael F and Mackay, Mark T and Majdan, Marek and Malekzadeh, Reza and Marcenes, Wagner and Margolis, David J and Margono, Christopher and Marzan, Melvin B and Masci, Joseph R and Mashal, Mohammad T and Matzopoulos, Richard and Mayosi, Bongani M and Mazorodze, Tasara T and Mcgill, Neil W and McGrath, John J and McKee, Martin and McLain, Abigail and Meaney, Peter A and Medina, Catalina and Mehndiratta, Man Mohan and Mekonnen, Wubegzier and Melaku, Yohannes A and Meltzer, Michele and Memish, Ziad A and Mensah, George A and Meretoja, Atte and Mhimbira, Francis A and Micha, Renata and Miller, Ted R and Mills, Edward J and Mitchell, Philip B and Mock, Charles N and Mohamed Ibrahim, Norlinah and Mohammad, Karzan A and Mokdad, Ali H and Mola, Glen L D and Monasta, Lorenzo and Monta{\~n}ez Hernandez, Julio C and Montico, Marcella and Montine, Thomas J and Mooney, Meghan D and Moore, Ami R and Moradi-Lakeh, Maziar and Moran, Andrew E and Mori, Rintaro and Moschandreas, Joanna and Moturi, Wilkister N and Moyer, Madeline L and Mozaffarian, Dariush and Msemburi, William T and Mueller, Ulrich O and Mukaigawara, Mitsuru and Mullany, Erin C and Murdoch, Michele E and Murray, Joseph and Murthy, Kinnari S and Naghavi, Mohsen and Naheed, Aliya and Naidoo, Kovin S and Naldi, Luigi and Nand, Devina and Nangia, Vinay and Narayan, K M Venkat and Nejjari, Chakib and Neupane, Sudan P and Newton, Charles R and Ng, Marie and Ngalesoni, Frida N and Nguyen, Grant and Nisar, Muhammad I and Nolte, Sandra and Norheim, Ole F and Norman, Rosana E and Norrving, Bo and Nyakarahuka, Luke and Oh, In-Hwan and Ohkubo, Takayoshi and Ohno, Summer L and Olusanya, Bolajoko O and Opio, John Nelson and Ortblad, Katrina and Ortiz, Alberto and Pain, Amanda W and Pandian, Jeyaraj D and Panelo, Carlo Irwin A and Papachristou, Christina and Park, Eun-Kee and Park, Jae-Hyun and Patten, Scott B and Patton, George C and Paul, Vinod K and Pavlin, Boris I and Pearce, Neil and Pereira, David M and Perez-Padilla, Rogelio and Perez-Ruiz, Fernando and Perico, Norberto and Pervaiz, Aslam and Pesudovs, Konrad and Peterson, Carrie B and Petzold, Max and Phillips, Michael R and Phillips, Bryan K and Phillips, David E and Piel, Fr{\'e}d{\'e}ric B and Plass, Dietrich and Poenaru, Dan and Polinder, Suzanne and Pope, Daniel and Popova, Svetlana and Poulton, Richie G and Pourmalek, Farshad and Prabhakaran, Dorairaj and Prasad, Noela M and Pullan, Rachel L and Qato, Dima M and Quistberg, D Alex and Rafay, Anwar and Rahimi, Kazem and Rahman, Sajjad U and Raju, Murugesan and Rana, Saleem M and Razavi, Homie and Reddy, K Srinath and Refaat, Amany and Remuzzi, Giuseppe and Resnikoff, Serge and Ribeiro, Antonio L and Richardson, Lee and Richardus, Jan Hendrik and Roberts, D Allen and Rojas-Rueda, David and Ronfani, Luca and Roth, Gregory A and Rothenbacher, Dietrich and Rothstein, David H and Rowley, Jane T and Roy, Nobhojit and Ruhago, George M and Saeedi, Mohammad Y and Saha, Sukanta and Sahraian, Mohammad Ali and Sampson, Uchechukwu K A and Sanabria, Juan R and Sandar, Logan and Santos, Itamar S and Satpathy, Maheswar and Sawhney, Monika and Scarborough, Peter and Schneider, Ione J and Sch{\"o}ttker, Ben and Schumacher, Austin E and Schwebel, David C and Scott, James G and Seedat, Soraya and Sepanlou, Sadaf G and Serina, Peter T and Servan-Mori, Edson E and Shackelford, Katya A and Shaheen, Amira and Shahraz, Saeid and Shamah Levy, Teresa and Shangguan, Siyi and She, Jun and Sheikhbahaei, Sara and Shi, Peilin and Shibuya, Kenji and Shinohara, Yukito and Shiri, Rahman and Shishani, Kawkab and Shiue, Ivy and Shrime, Mark G and Sigfusdottir, Inga D and Silberberg, Donald H and Simard, Edgar P and Sindi, Shireen and Singh, Abhishek and Singh, Jasvinder A and Singh, Lavanya and Skirbekk, Vegard and Slepak, Erica Leigh and Sliwa, Karen and Soneji, Samir and S{\o}reide, Kjetil and Soshnikov, Sergey and Sposato, Luciano A and Sreeramareddy, Chandrashekhar T and Stanaway, Jeffrey D and Stathopoulou, Vasiliki and Stein, Dan J and Stein, Murray B and Steiner, Caitlyn and Steiner, Timothy J and Stevens, Antony and Stewart, Andrea and Stovner, Lars J and Stroumpoulis, Konstantinos and Sunguya, Bruno F and Swaminathan, Soumya and Swaroop, Mamta and Sykes, Bryan L and Tabb, Karen M and Takahashi, Ken and Tandon, Nikhil and Tanne, David and Tanner, Marcel and Tavakkoli, Mohammad and Taylor, Hugh R and Te Ao, Braden J and Tediosi, Fabrizio and Temesgen, Awoke M and Templin, Tara and Ten Have, Margreet and Tenkorang, Eric Y and Terkawi, Abdullah S and Thomson, Blake and Thorne-Lyman, Andrew L and Thrift, Amanda G and Thurston, George D and Tillmann, Taavi and Tonelli, Marcello and Topouzis, Fotis and Toyoshima, Hideaki and Traebert, Jefferson and Tran, Bach X and Trillini, Matias and Truelsen, Thomas and Tsilimbaris, Miltiadis and Tuzcu, Emin M and Uchendu, Uche S and Ukwaja, Kingsley N and Undurraga, Eduardo A and Uzun, Selen B and Van Brakel, Wim H and van de Vijver, Steven and van Gool, Coen H and van Os, Jim and Vasankari, Tommi J and Venketasubramanian, N and Violante, Francesco S and Vlassov, Vasiliy V and Vollset, Stein Emil and Wagner, Gregory R and Wagner, Joseph and Waller, Stephen G and Wan, Xia and Wang, Haidong and Wang, JianLi and Wang, Linhong and Warouw, Tati S and Weichenthal, Scott and Weiderpass, Elisabete and Weintraub, Robert G and Wenzhi, Wang and Werdecker, Andrea and Westerman, Ronny and Whiteford, Harvey A and Wilkinson, James D and Williams, Thomas N and Wolfe, Charles D and Wolock, Timothy M and Woolf, Anthony D and Wulf, Sarah and Wurtz, Brittany and Xu, Gelin and Yan, Lijing L and Yano, Yuichiro and Ye, Pengpeng and Yent{\"u}r, G{\"o}kalp K and Yip, Paul and Yonemoto, Naohiro and Yoon, Seok-Jun and Younis, Mustafa Z and Yu, Chuanhua and Zaki, Maysaa E and Zhao, Yong and Zheng, Yingfeng and Zonies, David and Zou, Xiaonong and Salomon, Joshua A and Lopez, Alan D and Vos, Theo} } @article {8095, title = {Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis brazilian patients.}, journal = {Mol Biol Rep}, year = {2015}, month = {2015 Dec 19}, abstract = {

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value~=~0.0026, OR 1.31 and p value~=~0.0091, OR 1.28 with statistical power~=~0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA.

}, issn = {1573-4978}, doi = {10.1007/s11033-015-3937-z}, author = {Cavalcanti, Catarina Addobbati Jord{\~a}o and De Azev{\^e}do Silva, Jaqueline and de Barros Pita, Will and Veit, Tiago Degani and Monticielo, Odirlei Andre and Xavier, Ricardo Machado and Brenol, Jo{\~a}o Carlos Tavares and Brenol, Cleiton Viegas and Fragoso, Thiago Sotero and Barbosa, Alexandre Domingues and Duarte, {\^A}ngela Luiza Branco Pinto and Oliveira, Ren{\^e} Donizeti Ribeiro and Louzada-J{\'u}nior, Paulo and Donadi, Eduardo Ant{\^o}nio and Crovella, Sergio and Chies, Jos{\'e} Artur Bogo and Sandrin-Garcia, Paula} } @article {3576, title = {Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.}, journal = {Lancet}, volume = {384}, year = {2014}, month = {2014 Sep 13}, pages = {1005-70}, abstract = {

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

FINDINGS: Globally in 2013, there were 1{\textperiodcentered}8 million new HIV infections (95\% uncertainty interval 1{\textperiodcentered}7 million to 2{\textperiodcentered}1 million), 29{\textperiodcentered}2 million prevalent HIV cases (28{\textperiodcentered}1 to 31{\textperiodcentered}7), and 1{\textperiodcentered}3 million HIV deaths (1{\textperiodcentered}3 to 1{\textperiodcentered}5). At the peak of the epidemic in 2005, HIV caused 1{\textperiodcentered}7 million deaths (1{\textperiodcentered}6 million to 1{\textperiodcentered}9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19{\textperiodcentered}1 million life-years (16{\textperiodcentered}6 million to 21{\textperiodcentered}5 million) have been saved, 70{\textperiodcentered}3\% (65{\textperiodcentered}4 to 76{\textperiodcentered}1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7{\textperiodcentered}5 million (7{\textperiodcentered}4 million to 7{\textperiodcentered}7 million), prevalence was 11{\textperiodcentered}9 million (11{\textperiodcentered}6 million to 12{\textperiodcentered}2 million), and number of deaths was 1{\textperiodcentered}4 million (1{\textperiodcentered}3 million to 1{\textperiodcentered}5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7{\textperiodcentered}1 million (6{\textperiodcentered}9 million to 7{\textperiodcentered}3 million), prevalence was 11{\textperiodcentered}2 million (10{\textperiodcentered}8 million to 11{\textperiodcentered}6 million), and number of deaths was 1{\textperiodcentered}3 million (1{\textperiodcentered}2 million to 1{\textperiodcentered}4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64{\textperiodcentered}0\% of cases (63{\textperiodcentered}6 to 64{\textperiodcentered}3) and 64{\textperiodcentered}7\% of deaths (60{\textperiodcentered}8 to 70{\textperiodcentered}3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1{\textperiodcentered}2 million deaths (1{\textperiodcentered}1 million to 1{\textperiodcentered}4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31{\textperiodcentered}5\% (15{\textperiodcentered}7 to 44{\textperiodcentered}1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

INTERPRETATION: Our estimates of the number of people living with HIV are 18{\textperiodcentered}7\% smaller than UNAIDS{\textquoteright}s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

FUNDING: Bill \& Melinda Gates Foundation.

}, keywords = {Age Distribution, Epidemics, Female, Global Health, HIV Infections, Humans, Incidence, Malaria, Male, Mortality, Organizational Objectives, Sex Distribution, Tuberculosis}, issn = {1474-547X}, doi = {10.1016/S0140-6736(14)60844-8}, author = {Murray, Christopher J L and Ortblad, Katrina F and Guinovart, Caterina and Lim, Stephen S and Wolock, Timothy M and Roberts, D Allen and Dansereau, Emily A and Graetz, Nicholas and Barber, Ryan M and Brown, Jonathan C and Wang, Haidong and Duber, Herbert C and Naghavi, Mohsen and Dicker, Daniel and Dandona, Lalit and Salomon, Joshua A and Heuton, Kyle R and Foreman, Kyle and Phillips, David E and Fleming, Thomas D and Flaxman, Abraham D and Phillips, Bryan K and Johnson, Elizabeth K and Coggeshall, Megan S and Abd-Allah, Foad and Abera, Semaw Ferede and Abraham, Jerry P and Abubakar, Ibrahim and Abu-Raddad, Laith J and Abu-Rmeileh, Niveen Me and Achoki, Tom and Adeyemo, Austine Olufemi and Adou, Ars{\`e}ne Kouablan and Adsuar, Jos{\'e} C and Agardh, Emilie Elisabet and Akena, Dickens and Al Kahbouri, Mazin J and Alasfoor, Deena and Albittar, Mohammed I and Alcal{\'a}-Cerra, Gabriel and Alegretti, Miguel Angel and Alemu, Zewdie Aderaw and Alfonso-Cristancho, Rafael and Alhabib, Samia and Ali, Raghib and Alla, Fran{\c c}ois and Allen, Peter J and Alsharif, Ubai and Alvarez, Elena and Alvis-Guzm{\'a}n, Nelson and Amankwaa, Adansi A and Amare, Azmeraw T and Amini, Hassan and Ammar, Walid and Anderson, Benjamin O and Antonio, Carl Abelardo T and Anwari, Palwasha and Arnl{\"o}v, Johan and Arsenijevic, Valentina S Arsic and Artaman, Ali and Asghar, Rana J and Assadi, Reza and Atkins, Lydia S and Badawi, Alaa and Balakrishnan, Kalpana and Banerjee, Amitava and Basu, Sanjay and Beardsley, Justin and Bekele, Tolesa and Bell, Michelle L and Bernabe, Eduardo and Beyene, Tariku Jibat and Bhala, Neeraj and Bhalla, Ashish and Bhutta, Zulfiqar A and Abdulhak, Aref Bin and Binagwaho, Agnes and Blore, Jed D and Basara, Berrak Bora and Bose, Dipan and Brainin, Michael and Breitborde, Nicholas and Casta{\~n}eda-Orjuela, Carlos A and Catal{\'a}-L{\'o}pez, Ferr{\'a}n and Chadha, Vineet K and Chang, Jung-Chen and Chiang, Peggy Pei-Chia and Chuang, Ting-Wu and Colomar, Mercedes and Cooper, Leslie Trumbull and Cooper, Cyrus and Courville, Karen J and Cowie, Benjamin C and Criqui, Michael H and Dandona, Rakhi and Dayama, Anand and De Leo, Diego and Degenhardt, Louisa and del Pozo-Cruz, Borja and Deribe, Kebede and Des Jarlais, Don C and Dessalegn, Muluken and Dharmaratne, Samath D and Dilmen, U{\u g}ur and Ding, Eric L and Driscoll, Tim R and Durrani, Adnan M and Ellenbogen, Richard G and Ermakov, Sergey Petrovich and Esteghamati, Alireza and Faraon, Emerito Jose A and Farzadfar, Farshad and Fereshtehnejad, Seyed-Mohammad and Fijabi, Daniel Obadare and Forouzanfar, Mohammad H and Fra Paleo, Urbano and Gaffikin, Lynne and Gamkrelidze, Amiran and Gankp{\'e}, Fortun{\'e} Gb{\`e}toho and Geleijnse, Johanna M and Gessner, Bradford D and Gibney, Katherine B and Ginawi, Ibrahim Abdelmageem Mohamed and Glaser, Elizabeth L and Gona, Philimon and Goto, Atsushi and Gouda, Hebe N and Gugnani, Harish Chander and Gupta, Rajeev and Gupta, Rahul and Hafezi-Nejad, Nima and Hamadeh, Randah Ribhi and Hammami, Mouhanad and Hankey, Graeme J and Harb, Hilda L and Haro, Josep Maria and Havmoeller, Rasmus and Hay, Simon I and Hedayati, Mohammad T and Pi, Ileana B Heredia and Hoek, Hans W and Hornberger, John C and Hosgood, H Dean and Hotez, Peter J and Hoy, Damian G and Huang, John J and Iburg, Kim M and Idrisov, Bulat T and Innos, Kaire and Jacobsen, Kathryn H and Jeemon, Panniyammakal and Jensen, Paul N and Jha, Vivekanand and Jiang, Guohong and Jonas, Jost B and Juel, Knud and Kan, Haidong and Kankindi, Ida and Karam, Nadim E and Karch, Andr{\'e} and Karema, Corine Kakizi and Kaul, Anil and Kawakami, Norito and Kazi, Dhruv S and Kemp, Andrew H and Kengne, Andre Pascal and Keren, Andre and Kereselidze, Maia and Khader, Yousef Saleh and Khalifa, Shams Eldin Ali Hassan and Khan, Ejaz Ahmed and Khang, Young-Ho and Khonelidze, Irma and Kinfu, Yohannes and Kinge, Jonas M and Knibbs, Luke and Kokubo, Yoshihiro and Kosen, S and Defo, Barthelemy Kuate and Kulkarni, Veena S and Kulkarni, Chanda and Kumar, Kaushalendra and Kumar, Ravi B and Kumar, G Anil and Kwan, Gene F and Lai, Taavi and Balaji, Arjun Lakshmana and Lam, Hilton and Lan, Qing and Lansingh, Van C and Larson, Heidi J and Larsson, Anders and Lee, Jong-Tae and Leigh, James and Leinsalu, Mall and Leung, Ricky and Li, Yichong and Li, Yongmei and de Lima, Gra{\c c}a Maria Ferreira and Lin, Hsien-Ho and Lipshultz, Steven E and Liu, Shiwei and Liu, Yang and Lloyd, Belinda K and Lotufo, Paulo A and Machado, Vasco Manuel Pedro and Maclachlan, Jennifer H and Magis-Rodriguez, Carlos and Majdan, Marek and Mapoma, Christopher Chabila and Marcenes, Wagner and Marzan, Melvin Barrientos and Masci, Joseph R and Mashal, Mohammad Taufiq and Mason-Jones, Amanda J and Mayosi, Bongani M and Mazorodze, Tasara T and Mckay, Abigail Cecilia and Meaney, Peter A and Mehndiratta, Man Mohan and Mejia-Rodriguez, Fabiola and Melaku, Yohannes Adama and Memish, Ziad A and Mendoza, Walter and Miller, Ted R and Mills, Edward J and Mohammad, Karzan Abdulmuhsin and Mokdad, Ali H and Mola, Glen Liddell and Monasta, Lorenzo and Montico, Marcella and Moore, Ami R and Mori, Rintaro and Moturi, Wilkister Nyaora and Mukaigawara, Mitsuru and Murthy, Kinnari S and Naheed, Aliya and Naidoo, Kovin S and Naldi, Luigi and Nangia, Vinay and Narayan, K M Venkat and Nash, Denis and Nejjari, Chakib and Nelson, Robert G and Neupane, Sudan Prasad and Newton, Charles R and Ng, Marie and Nisar, Muhammad Imran and Nolte, Sandra and Norheim, Ole F and Nowaseb, Vincent and Nyakarahuka, Luke and Oh, In-Hwan and Ohkubo, Takayoshi and Olusanya, Bolajoko O and Omer, Saad B and Opio, John Nelson and Orisakwe, Orish Ebere and Pandian, Jeyaraj D and Papachristou, Christina and Caicedo, Angel J Paternina and Patten, Scott B and Paul, Vinod K and Pavlin, Boris Igor and Pearce, Neil and Pereira, David M and Pervaiz, Aslam and Pesudovs, Konrad and Petzold, Max and Pourmalek, Farshad and Qato, Dima and Quezada, Amado D and Quistberg, D Alex and Rafay, Anwar and Rahimi, Kazem and Rahimi-Movaghar, Vafa and ur Rahman, Sajjad and Raju, Murugesan and Rana, Saleem M and Razavi, Homie and Reilly, Robert Quentin and Remuzzi, Giuseppe and Richardus, Jan Hendrik and Ronfani, Luca and Roy, Nobhojit and Sabin, Nsanzimana and Saeedi, Mohammad Yahya and Sahraian, Mohammad Ali and Samonte, Genesis May J and Sawhney, Monika and Schneider, Ione J C and Schwebel, David C and Seedat, Soraya and Sepanlou, Sadaf G and Servan-Mori, Edson E and Sheikhbahaei, Sara and Shibuya, Kenji and Shin, Hwashin Hyun and Shiue, Ivy and Shivakoti, Rupak and Sigfusdottir, Inga Dora and Silberberg, Donald H and Silva, Andrea P and Simard, Edgar P and Singh, Jasvinder A and Skirbekk, Vegard and Sliwa, Karen and Soneji, Samir and Soshnikov, Sergey S and Sreeramareddy, Chandrashekhar T and Stathopoulou, Vasiliki Kalliopi and Stroumpoulis, Konstantinos and Swaminathan, Soumya and Sykes, Bryan L and Tabb, Karen M and Talongwa, Roberto Tchio and Tenkorang, Eric Yeboah and Terkawi, Abdullah Sulieman and Thomson, Alan J and Thorne-Lyman, Andrew L and Towbin, Jeffrey A and Traebert, Jefferson and Tran, Bach X and Dimbuene, Zacharie Tsala and Tsilimbaris, Miltiadis and Uchendu, Uche S and Ukwaja, Kingsley N and Uzun, Selen Beg{\"u}m and Vallely, Andrew J and Vasankari, Tommi J and Venketasubramanian, N and Violante, Francesco S and Vlassov, Vasiliy Victorovich and Vollset, Stein Emil and Waller, Stephen and Wallin, Mitchell T and Wang, Linhong and Wang, XiaoRong and Wang, Yanping and Weichenthal, Scott and Weiderpass, Elisabete and Weintraub, Robert G and Westerman, Ronny and White, Richard A and Wilkinson, James D and Williams, Thomas Neil and Woldeyohannes, Solomon Meseret and Wong, John Q and Xu, Gelin and Yang, Yang C and Yano, Yuichiro and Yentur, Gokalp Kadri and Yip, Paul and Yonemoto, Naohiro and Yoon, Seok-Jun and Younis, Mustafa and Yu, Chuanhua and Jin, Kim Yun and El Sayed Zaki, Maysaa and Zhao, Yong and Zheng, Yingfeng and Zhou, Maigeng and Zhu, Jun and Zou, Xiao Nong and Lopez, Alan D and Vos, Theo} } @article {3531, title = {Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.}, journal = {Lancet}, volume = {384}, year = {2014}, month = {2014 Sep 13}, pages = {980-1004}, abstract = {

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75\% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.

METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95\% uncertainty intervals (UIs) for all values.

FINDINGS: 292,982 (95\% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0{\textperiodcentered}3\% (-1{\textperiodcentered}1 to 0{\textperiodcentered}6) from 1990 to 2003, and -2{\textperiodcentered}7\% (-3{\textperiodcentered}9 to -1{\textperiodcentered}5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0{\textperiodcentered}4\% (0{\textperiodcentered}2-0{\textperiodcentered}6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956{\textperiodcentered}8 (685{\textperiodcentered}1-1262{\textperiodcentered}8) in South Sudan to 2{\textperiodcentered}4 (1{\textperiodcentered}6-3{\textperiodcentered}6) in Iceland.

INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

FUNDING: Bill \& Melinda Gates Foundation.

}, keywords = {Age Distribution, Cause of Death, Female, Global Health, HIV Infections, Humans, Maternal Mortality, Models, Statistical, Organizational Objectives, Pregnancy, Pregnancy Complications, Infectious, Risk Factors, Socioeconomic Factors, Time Factors}, issn = {1474-547X}, doi = {10.1016/S0140-6736(14)60696-6}, author = {Kassebaum, Nicholas J and Bertozzi-Villa, Amelia and Coggeshall, Megan S and Shackelford, Katya A and Steiner, Caitlyn and Heuton, Kyle R and Gonzalez-Medina, Diego and Barber, Ryan and Huynh, Chantal and Dicker, Daniel and Templin, Tara and Wolock, Timothy M and Ozgoren, Ayse Abbasoglu and Abd-Allah, Foad and Abera, Semaw Ferede and Abubakar, Ibrahim and Achoki, Tom and Adelekan, Ademola and Ademi, Zanfina and Adou, Ars{\`e}ne Kouablan and Adsuar, Jos{\'e} C and Agardh, Emilie E and Akena, Dickens and Alasfoor, Deena and Alemu, Zewdie Aderaw and Alfonso-Cristancho, Rafael and Alhabib, Samia and Ali, Raghib and Al Kahbouri, Mazin J and Alla, Fran{\c c}ois and Allen, Peter J and AlMazroa, Mohammad A and Alsharif, Ubai and Alvarez, Elena and Alvis-Guzm{\'a}n, Nelson and Amankwaa, Adansi A and Amare, Azmeraw T and Amini, Hassan and Ammar, Walid and Antonio, Carl A T and Anwari, Palwasha and Arnl{\"o}v, Johan and Arsenijevic, Valentina S Arsic and Artaman, Ali and Asad, Majed Masoud and Asghar, Rana J and Assadi, Reza and Atkins, Lydia S and Badawi, Alaa and Balakrishnan, Kalpana and Basu, Arindam and Basu, Sanjay and Beardsley, Justin and Bedi, Neeraj and Bekele, Tolesa and Bell, Michelle L and Bernabe, Eduardo and Beyene, Tariku J and Bhutta, Zulfiqar and Bin Abdulhak, Aref and Blore, Jed D and Basara, Berrak Bora and Bose, Dipan and Breitborde, Nicholas and C{\'a}rdenas, Rosario and Casta{\~n}eda-Orjuela, Carlos A and Castro, Ruben Estanislao and Catal{\'a}-L{\'o}pez, Ferr{\'a}n and Cavlin, Alanur and Chang, Jung-Chen and Che, Xuan and Christophi, Costas A and Chugh, Sumeet S and Cirillo, Massimo and Colquhoun, Samantha M and Cooper, Leslie Trumbull and Cooper, Cyrus and da Costa Leite, Iuri and Dandona, Lalit and Dandona, Rakhi and Davis, Adrian and Dayama, Anand and Degenhardt, Louisa and De Leo, Diego and del Pozo-Cruz, Borja and Deribe, Kebede and Dessalegn, Muluken and deVeber, Gabrielle A and Dharmaratne, Samath D and Dilmen, U{\u g}ur and Ding, Eric L and Dorrington, Rob E and Driscoll, Tim R and Ermakov, Sergei Petrovich and Esteghamati, Alireza and Faraon, Emerito Jose A and Farzadfar, Farshad and Felicio, Manuela Mendonca and Fereshtehnejad, Seyed-Mohammad and de Lima, Gra{\c c}a Maria Ferreira and Forouzanfar, Mohammad H and Fran{\c c}a, Elisabeth B and Gaffikin, Lynne and Gambashidze, Ketevan and Gankp{\'e}, Fortun{\'e} Gb{\`e}toho and Garcia, Ana C and Geleijnse, Johanna M and Gibney, Katherine B and Giroud, Maurice and Glaser, Elizabeth L and Goginashvili, Ketevan and Gona, Philimon and Gonz{\'a}lez-Castell, Dinorah and Goto, Atsushi and Gouda, Hebe N and Gugnani, Harish Chander and Gupta, Rahul and Gupta, Rajeev and Hafezi-Nejad, Nima and Hamadeh, Randah Ribhi and Hammami, Mouhanad and Hankey, Graeme J and Harb, Hilda L and Havmoeller, Rasmus and Hay, Simon I and Pi, Ileana B Heredia and Hoek, Hans W and Hosgood, H Dean and Hoy, Damian G and Husseini, Abdullatif and Idrisov, Bulat T and Innos, Kaire and Inoue, Manami and Jacobsen, Kathryn H and Jahangir, Eiman and Jee, Sun Ha and Jensen, Paul N and Jha, Vivekanand and Jiang, Guohong and Jonas, Jost B and Juel, Knud and Kabagambe, Edmond Kato and Kan, Haidong and Karam, Nadim E and Karch, Andr{\'e} and Karema, Corine Kakizi and Kaul, Anil and Kawakami, Norito and Kazanjan, Konstantin and Kazi, Dhruv S and Kemp, Andrew H and Kengne, Andre Pascal and Kereselidze, Maia and Khader, Yousef Saleh and Khalifa, Shams Eldin Ali Hassan and Khan, Ejaz Ahmed and Khang, Young-Ho and Knibbs, Luke and Kokubo, Yoshihiro and Kosen, Soewarta and Defo, Barthelemy Kuate and Kulkarni, Chanda and Kulkarni, Veena S and Kumar, G Anil and Kumar, Kaushalendra and Kumar, Ravi B and Kwan, Gene and Lai, Taavi and Lalloo, Ratilal and Lam, Hilton and Lansingh, Van C and Larsson, Anders and Lee, Jong-Tae and Leigh, James and Leinsalu, Mall and Leung, Ricky and Li, Xiaohong and Li, Yichong and Li, Yongmei and Liang, Juan and Liang, Xiaofeng and Lim, Stephen S and Lin, Hsien-Ho and Lipshultz, Steven E and Liu, Shiwei and Liu, Yang and Lloyd, Belinda K and London, Stephanie J and Lotufo, Paulo A and Ma, Jixiang and Ma, Stefan and Machado, Vasco Manuel Pedro and Mainoo, Nana Kwaku and Majdan, Marek and Mapoma, Christopher Chabila and Marcenes, Wagner and Marzan, Melvin Barrientos and Mason-Jones, Amanda J and Mehndiratta, Man Mohan and Mejia-Rodriguez, Fabiola and Memish, Ziad A and Mendoza, Walter and Miller, Ted R and Mills, Edward J and Mokdad, Ali H and Mola, Glen Liddell and Monasta, Lorenzo and de la Cruz Monis, Jonathan and Hernandez, Julio Cesar Monta{\~n}ez and Moore, Ami R and Moradi-Lakeh, Maziar and Mori, Rintaro and Mueller, Ulrich O and Mukaigawara, Mitsuru and Naheed, Aliya and Naidoo, Kovin S and Nand, Devina and Nangia, Vinay and Nash, Denis and Nejjari, Chakib and Nelson, Robert G and Neupane, Sudan Prasad and Newton, Charles R and Ng, Marie and Nieuwenhuijsen, Mark J and Nisar, Muhammad Imran and Nolte, Sandra and Norheim, Ole F and Nyakarahuka, Luke and Oh, In-Hwan and Ohkubo, Takayoshi and Olusanya, Bolajoko O and Omer, Saad B and Opio, John Nelson and Orisakwe, Orish Ebere and Pandian, Jeyaraj D and Papachristou, Christina and Park, Jae-Hyun and Caicedo, Angel J Paternina and Patten, Scott B and Paul, Vinod K and Pavlin, Boris Igor and Pearce, Neil and Pereira, David M and Pesudovs, Konrad and Petzold, Max and Poenaru, Dan and Polanczyk, Guilherme V and Polinder, Suzanne and Pope, Dan and Pourmalek, Farshad and Qato, Dima and Quistberg, D Alex and Rafay, Anwar and Rahimi, Kazem and Rahimi-Movaghar, Vafa and ur Rahman, Sajjad and Raju, Murugesan and Rana, Saleem M and Refaat, Amany and Ronfani, Luca and Roy, Nobhojit and Pimienta, Tania Georgina S{\'a}nchez and Sahraian, Mohammad Ali and Salomon, Joshua A and Sampson, Uchechukwu and Santos, Itamar S and Sawhney, Monika and Sayinzoga, Felix and Schneider, Ione J C and Schumacher, Austin and Schwebel, David C and Seedat, Soraya and Sepanlou, Sadaf G and Servan-Mori, Edson E and Shakh-Nazarova, Marina and Sheikhbahaei, Sara and Shibuya, Kenji and Shin, Hwashin Hyun and Shiue, Ivy and Sigfusdottir, Inga Dora and Silberberg, Donald H and Silva, Andrea P and Singh, Jasvinder A and Skirbekk, Vegard and Sliwa, Karen and Soshnikov, Sergey S and Sposato, Luciano A and Sreeramareddy, Chandrashekhar T and Stroumpoulis, Konstantinos and Sturua, Lela and Sykes, Bryan L and Tabb, Karen M and Talongwa, Roberto Tchio and Tan, Feng and Teixeira, Carolina Maria and Tenkorang, Eric Yeboah and Terkawi, Abdullah Sulieman and Thorne-Lyman, Andrew L and Tirschwell, David L and Towbin, Jeffrey A and Tran, Bach X and Tsilimbaris, Miltiadis and Uchendu, Uche S and Ukwaja, Kingsley N and Undurraga, Eduardo A and Uzun, Selen Beg{\"u}m and Vallely, Andrew J and van Gool, Coen H and Vasankari, Tommi J and Vavilala, Monica S and Venketasubramanian, N and Villalpando, Salvador and Violante, Francesco S and Vlassov, Vasiliy Victorovich and Vos, Theo and Waller, Stephen and Wang, Haidong and Wang, Linhong and Wang, XiaoRong and Wang, Yanping and Weichenthal, Scott and Weiderpass, Elisabete and Weintraub, Robert G and Westerman, Ronny and Wilkinson, James D and Woldeyohannes, Solomon Meseret and Wong, John Q and Wordofa, Muluemebet Abera and Xu, Gelin and Yang, Yang C and Yano, Yuichiro and Yentur, Gokalp Kadri and Yip, Paul and Yonemoto, Naohiro and Yoon, Seok-Jun and Younis, Mustafa Z and Yu, Chuanhua and Jin, Kim Yun and El Sayed Zaki, Maysaa and Zhao, Yong and Zheng, Yingfeng and Zhou, Maigeng and Zhu, Jun and Zou, Xiao Nong and Lopez, Alan D and Naghavi, Mohsen and Murray, Christopher J L and Lozano, Rafael} } @article {1619, title = {Mannose-binding lectin gene (MBL-2) polymorphism in oral lichen planus.}, journal = {Clin Oral Investig}, volume = {15}, year = {2011}, month = {2011 Oct}, pages = {699-704}, abstract = {

TNF-α may be associated with the etiopathogenesis of oral lichen planus (OLP), and it has been suggested that polymorphism of mannose-binding lectin (MBL) increases the in vitro production of TNF- α. The aim of the present study was to assess the relevance of genetic diversity of MBL in OLP. The study sample comprised 90 individuals, 45 OLP patients and 45 healthy volunteers. MBL-2 gene was amplified using real-time PCR. Frequency of A/A genotype was 55.6\% in OLP and 53.3\% in healthy volunteers. Likewise, A/0 heterozygote genotype was found in 42.2\% and 35.6\%; 2.2\% and 11.1\%, had the recessive 0/0 genotype respectively. Frequencies of the "A" and "0" alleles were 77\% and 23\% in the OLP group and 71.2\% in control group. There were no statistically significant differences regarding genotype frequency (p = 0.546) or allele frequency (p = 0.497). In conclusion, no significant association was found between polymorphism of MBL-2 gene and OLP.

}, keywords = {Adolescent, Adult, Aged, Female, Gene Expression Regulation, Gene Frequency, Genes, Recessive, Genetic Variation, Genotype, Heterozygote, Homozygote, Humans, Lichen Planus, Oral, Male, Mannose-Binding Lectin, Middle Aged, Mutation, Polymorphism, Genetic, Real-Time Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, Young Adult}, issn = {1436-3771}, doi = {10.1007/s00784-010-0428-4}, author = {Barkokebas, Andreza and de Albuquerque T Carvalho, Alessandra and de Souza, Paulo Roberto Eleut{\'e}rio and Gomez, Ricardo Santiago and Xavier, Guilherme Machado and Ribeiro, Camila Maria Beder and Crovella, Sergio and Porter, Stephen Ross and Le{\~a}o, Jair Carneiro} }