%0 Journal Article %J Sci Rep %D 2017 %T 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function. %A Gorski, Mathias %A van der Most, Peter J %A Teumer, Alexander %A Chu, Audrey Y %A Li, Man %A Mijatovic, Vladan %A Nolte, Ilja M %A Cocca, Massimiliano %A Taliun, Daniel %A Gomez, Felicia %A Li, Yong %A Tayo, Bamidele %A Tin, Adrienne %A Feitosa, Mary F %A Aspelund, Thor %A Attia, John %A Biffar, Reiner %A Bochud, Murielle %A Boerwinkle, Eric %A Borecki, Ingrid %A Bottinger, Erwin P %A Chen, Ming-Huei %A Chouraki, Vincent %A Ciullo, Marina %A Coresh, Josef %A Cornelis, Marilyn C %A Curhan, Gary C %A d'Adamo, Adamo Pio %A Dehghan, Abbas %A Dengler, Laura %A Ding, Jingzhong %A Eiriksdottir, Gudny %A Endlich, Karlhans %A Enroth, Stefan %A Esko, Tõnu %A Franco, Oscar H %A Gasparini, Paolo %A Gieger, Christian %A Girotto, Giorgia %A Gottesman, Omri %A Gudnason, Vilmundur %A Gyllensten, Ulf %A Hancock, Stephen J %A Harris, Tamara B %A Helmer, Catherine %A Höllerer, Simon %A Hofer, Edith %A Hofman, Albert %A Holliday, Elizabeth G %A Homuth, Georg %A Hu, Frank B %A Huth, Cornelia %A Hutri-Kähönen, Nina %A Hwang, Shih-Jen %A Imboden, Medea %A Johansson, Åsa %A Kähönen, Mika %A König, Wolfgang %A Kramer, Holly %A Krämer, Bernhard K %A Kumar, Ashish %A Kutalik, Zoltán %A Lambert, Jean-Charles %A Launer, Lenore J %A Lehtimäki, Terho %A de Borst, Martin %A Navis, Gerjan %A Swertz, Morris %A Liu, Yongmei %A Lohman, Kurt %A Loos, Ruth J F %A Lu, Yingchang %A Lyytikäinen, Leo-Pekka %A McEvoy, Mark A %A Meisinger, Christa %A Meitinger, Thomas %A Metspalu, Andres %A Metzger, Marie %A Mihailov, Evelin %A Mitchell, Paul %A Nauck, Matthias %A Oldehinkel, Albertine J %A Olden, Matthias %A Wjh Penninx, Brenda %A Pistis, Giorgio %A Pramstaller, Peter P %A Probst-Hensch, Nicole %A Raitakari, Olli T %A Rettig, Rainer %A Ridker, Paul M %A Rivadeneira, Fernando %A Robino, Antonietta %A Rosas, Sylvia E %A Ruderfer, Douglas %A Ruggiero, Daniela %A Saba, Yasaman %A Sala, Cinzia %A Schmidt, Helena %A Schmidt, Reinhold %A Scott, Rodney J %A Sedaghat, Sanaz %A Smith, Albert V %A Sorice, Rossella %A Stengel, Bénédicte %A Stracke, Sylvia %A Strauch, Konstantin %A Toniolo, Daniela %A Uitterlinden, André G %A Ulivi, Sheila %A Viikari, Jorma S %A Völker, Uwe %A Vollenweider, Peter %A Völzke, Henry %A Vuckovic, Dragana %A Waldenberger, Melanie %A Jin Wang, Jie %A Yang, Qiong %A Chasman, Daniel I %A Tromp, Gerard %A Snieder, Harold %A Heid, Iris M %A Fox, Caroline S %A Köttgen, Anna %A Pattaro, Cristian %A Böger, Carsten A %A Fuchsberger, Christian %K Computational Biology %K Gene Frequency %K Genetic Loci %K Genome, Human %K Genome-Wide Association Study %K Genotyping Techniques %K Humans %K Kidney %K Polymorphism, Single Nucleotide %X

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

%B Sci Rep %V 7 %P 45040 %8 2017 04 28 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/28452372?dopt=Abstract %R 10.1038/srep45040 %0 Journal Article %J Mol Cytogenet %D 2015 %T Phenotypic and genetic characterization of a family carrying two Xq21.1-21.3 interstitial deletions associated with syndromic hearing loss. %A Iossa, Sandra %A Costa, Valerio %A Corvino, Virginia %A Auletta, Gennaro %A Barruffo, Luigi %A Cappellani, Stefania %A Ceglia, Carlo %A Cennamo, Giovanni %A d'Adamo, Adamo Pio %A D'Amico, Alessandra %A Di Paolo, Nilde %A Forte, Raimondo %A Gasparini, Paolo %A Laria, Carla %A Lombardo, Barbara %A Malesci, Rita %A Vitale, Andrea %A Marciano, Elio %A Franzè, Annamaria %X

BACKGROUND: Sensorineural hearing impairment is a common pathological manifestation in patients affected by X-linked intellectual disability. A few cases of interstitial deletions at Xq21 with several different phenotypic characteristics have been described, but to date, a complete molecular characterization of the deletions harboring disease-causing genes is still missing. Thus, the aim of this study is to realize a detailed clinical and molecular analysis of a family affected by syndromic X-linked hearing loss with intellectual disability.

RESULTS: Clinical analyses revealed a very complex phenotype that included inner ear malformations, vestibular problems, choroideremia and hypotonia with a peculiar pattern of phenotypic variability. Genomic analysis revealed, for the first time, the presence of two close interstitial deletions in the Xq21.1-21.3, harboring 11 protein coding, 9 non-coding genes and 19 pseudogenes. Among these, 3 protein coding genes have already been associated with X-linked hearing loss, intellectual disability and choroideremia.

CONCLUSIONS: In this study we highlighted the presence of peculiar genotypic and phenotypic details in a family affected by syndromic X-linked hearing loss with intellectual disability. We identified two, previously unreported, Xq21.1-21.3 interstitial deletions. The two rearrangements, containing several genes, segregate with the clinical features, suggesting their role in the pathogenicity. However, not all the observed phenotypic features can be clearly associated with the known genes thus, further study is necessary to determine regions involved.

%B Mol Cytogenet %V 8 %P 18 %8 2015 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/25821518?dopt=Abstract %R 10.1186/s13039-015-0120-0 %0 Journal Article %J Mutat Res %D 2015 %T Target sequencing approach intended to discover new mutations in non-syndromic intellectual disability. %A Morgan, Anna %A Gandin, Ilaria %A Belcaro, Chiara %A Palumbo, Pietro %A Palumbo, Orazio %A Biamino, Elisa %A Dal Col, Valentina %A Laurini, Erik %A Pricl, Sabrina %A Bosco, Paolo %A Carella, Massimo %A Ferrero, Giovanni Battista %A Romano, Corrado %A d'Adamo, Adamo Pio %A Faletra, Flavio %A Vozzi, Diego %X

The technological improvements over the last years made considerable progresses in the knowledge of the etiology of intellectual Disability (ID). However, at present very little is known about the genetic heterogeneity underlying the non-syndromic form of ID (NS-ID). To investigate the genetic basis of NS-ID we analyzed 43 trios and 22 isolated NS-ID patients using a targeted sequencing (TS) approach. 71 NS-ID genes have been selected and sequenced in all subjects. We found putative pathogenic mutations in 7 out of 65 patients. The pathogenic role of mutations was evaluated through sequence comparison and structural analysis was performed to predict the effect of alterations in a 3D computational model through molecular dynamics simulations. Additionally, a deep patient clinical re-evaluation has been performed after the molecular results. This approach allowed us to find novel pathogenic mutations with a detection rate close to 11% in our cohort of patients. This result supports the hypothesis that many NS-ID related genes still remain to be discovered and that NS-ID is a more complex phenotype compared to syndromic form, likely caused by a complex and broad interaction between genes alterations and environment factors.

%B Mutat Res %V 781 %P 32-6 %8 2015 Nov %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/26411299?dopt=Abstract %R 10.1016/j.mrfmmm.2015.09.002 %0 Journal Article %J Hum Mol Genet %D 2014 %T DNA mismatch repair gene MSH6 implicated in determining age at natural menopause. %A Perry, John R B %A Hsu, Yi-Hsiang %A Chasman, Daniel I %A Johnson, Andrew D %A Elks, Cathy %A Albrecht, Eva %A Andrulis, Irene L %A Beesley, Jonathan %A Berenson, Gerald S %A Bergmann, Sven %A Bojesen, Stig E %A Bolla, Manjeet K %A Brown, Judith %A Buring, Julie E %A Campbell, Harry %A Chang-Claude, Jenny %A Chenevix-Trench, Georgia %A Corre, Tanguy %A Couch, Fergus J %A Cox, Angela %A Czene, Kamila %A d'Adamo, Adamo Pio %A Davies, Gail %A Deary, Ian J %A Dennis, Joe %A Easton, Douglas F %A Engelhardt, Ellen G %A Eriksson, Johan G %A Esko, Tõnu %A Fasching, Peter A %A Figueroa, Jonine D %A Flyger, Henrik %A Fraser, Abigail %A Garcia-Closas, Montse %A Gasparini, Paolo %A Gieger, Christian %A Giles, Graham %A Guenel, Pascal %A Hägg, Sara %A Hall, Per %A Hayward, Caroline %A Hopper, John %A Ingelsson, Erik %A Kardia, Sharon L R %A Kasiman, Katherine %A Knight, Julia A %A Lahti, Jari %A Lawlor, Debbie A %A Magnusson, Patrik K E %A Margolin, Sara %A Marsh, Julie A %A Metspalu, Andres %A Olson, Janet E %A Pennell, Craig E %A Polasek, Ozren %A Rahman, Iffat %A Ridker, Paul M %A Robino, Antonietta %A Rudan, Igor %A Rudolph, Anja %A Salumets, Andres %A Schmidt, Marjanka K %A Schoemaker, Minouk J %A Smith, Erin N %A Smith, Jennifer A %A Southey, Melissa %A Stöckl, Doris %A Swerdlow, Anthony J %A Thompson, Deborah J %A Truong, Therese %A Ulivi, Sheila %A Waldenberger, Melanie %A Wang, Qin %A Wild, Sarah %A Wilson, James F %A Wright, Alan F %A Zgaga, Lina %A Ong, Ken K %A Murabito, Joanne M %A Karasik, David %A Murray, Anna %K Age Factors %K DNA-Binding Proteins %K Female %K Genome-Wide Association Study %K Humans %K Menopause %K Polymorphism, Single Nucleotide %X

The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to ∼50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 × 10(-9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.

%B Hum Mol Genet %V 23 %P 2490-7 %8 2014 May 1 %G eng %N 9 %1 http://www.ncbi.nlm.nih.gov/pubmed/24357391?dopt=Abstract %R 10.1093/hmg/ddt620 %0 Journal Article %J Gene %D 2014 %T A novel P2RX2 mutation in an Italian family affected by autosomal dominant nonsyndromic hearing loss. %A Faletra, Flavio %A Girotto, Giorgia %A d'Adamo, Adamo Pio %A Vozzi, Diego %A Morgan, Anna %A Gasparini, Paolo %K Amino Acid Sequence %K Deafness %K European Continental Ancestry Group %K Female %K Genotype %K Hearing Loss, Sensorineural %K Humans %K Italy %K Male %K Molecular Sequence Data %K Mutation, Missense %K Pedigree %K Receptors, Purinergic P2X2 %X

Hereditary hearing loss (HHL) is a common disorder accounting for at least 60% of prelingual deafness. It is characterized by a large genetic heterogeneity, and despite the presence of a major gene, still there is a need to search for new causative mutations/genes. Very recently, a mutation within ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) gene (P2RX2) at DNFA41 locus has been reported leading to a bilateral and symmetrical sensorineural non-syndromic autosomal dominant HHL in two Chinese families. We performed a linkage analysis in a large Italian family with a dominant pattern of inheritance showing a significant 3.31 LOD score in a 2Mb region overlapping with the DNFA41 locus. Molecular analyses of P2RX2 identified a novel missense mutation (p.Gly353Arg) affecting a residue highly conserved across species. Visual inspection of the protein structure as obtained from comparative modeling suggests that substitution of the small glycine residue with a charged bulky residue such as an arginine that is close to the 'neck' of the region responsible for ion channel gating should have a high energetic cost and should lead to a severely destabilization of the fold. The identification of a second most likely causative mutation in P2RX2 gene further supports the possible role of this gene in causing autosomal dominant HHL.

%B Gene %V 534 %P 236-9 %8 2014 Jan 25 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/24211385?dopt=Abstract %R 10.1016/j.gene.2013.10.052 %0 Journal Article %J Nature %D 2014 %T Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. %A Perry, John R B %A Day, Felix %A Elks, Cathy E %A Sulem, Patrick %A Thompson, Deborah J %A Ferreira, Teresa %A He, Chunyan %A Chasman, Daniel I %A Esko, Tõnu %A Thorleifsson, Gudmar %A Albrecht, Eva %A Ang, Wei Q %A Corre, Tanguy %A Cousminer, Diana L %A Feenstra, Bjarke %A Franceschini, Nora %A Ganna, Andrea %A Johnson, Andrew D %A Kjellqvist, Sanela %A Lunetta, Kathryn L %A McMahon, George %A Nolte, Ilja M %A Paternoster, Lavinia %A Porcu, Eleonora %A Smith, Albert V %A Stolk, Lisette %A Teumer, Alexander %A Tšernikova, Natalia %A Tikkanen, Emmi %A Ulivi, Sheila %A Wagner, Erin K %A Amin, Najaf %A Bierut, Laura J %A Byrne, Enda M %A Hottenga, Jouke-Jan %A Koller, Daniel L %A Mangino, Massimo %A Pers, Tune H %A Yerges-Armstrong, Laura M %A Hua Zhao, Jing %A Andrulis, Irene L %A Anton-Culver, Hoda %A Atsma, Femke %A Bandinelli, Stefania %A Beckmann, Matthias W %A Benitez, Javier %A Blomqvist, Carl %A Bojesen, Stig E %A Bolla, Manjeet K %A Bonanni, Bernardo %A Brauch, Hiltrud %A Brenner, Hermann %A Buring, Julie E %A Chang-Claude, Jenny %A Chanock, Stephen %A Chen, Jinhui %A Chenevix-Trench, Georgia %A Collée, J Margriet %A Couch, Fergus J %A Couper, David %A Coviello, Andrea D %A Cox, Angela %A Czene, Kamila %A d'Adamo, Adamo Pio %A Davey Smith, George %A De Vivo, Immaculata %A Demerath, Ellen W %A Dennis, Joe %A Devilee, Peter %A Dieffenbach, Aida K %A Dunning, Alison M %A Eiriksdottir, Gudny %A Eriksson, Johan G %A Fasching, Peter A %A Ferrucci, Luigi %A Flesch-Janys, Dieter %A Flyger, Henrik %A Foroud, Tatiana %A Franke, Lude %A Garcia, Melissa E %A García-Closas, Montserrat %A Geller, Frank %A de Geus, Eco E J %A Giles, Graham G %A Gudbjartsson, Daniel F %A Gudnason, Vilmundur %A Guenel, Pascal %A Guo, Suiqun %A Hall, Per %A Hamann, Ute %A Haring, Robin %A Hartman, Catharina A %A Heath, Andrew C %A Hofman, Albert %A Hooning, Maartje J %A Hopper, John L %A Hu, Frank B %A Hunter, David J %A Karasik, David %A Kiel, Douglas P %A Knight, Julia A %A Kosma, Veli-Matti %A Kutalik, Zoltán %A Lai, Sandra %A Lambrechts, Diether %A Lindblom, Annika %A Mägi, Reedik %A Magnusson, Patrik K %A Mannermaa, Arto %A Martin, Nicholas G %A Masson, Gisli %A McArdle, Patrick F %A McArdle, Wendy L %A Melbye, Mads %A Michailidou, Kyriaki %A Mihailov, Evelin %A Milani, Lili %A Milne, Roger L %A Nevanlinna, Heli %A Neven, Patrick %A Nohr, Ellen A %A Oldehinkel, Albertine J %A Oostra, Ben A %A Palotie, Aarno %A Peacock, Munro %A Pedersen, Nancy L %A Peterlongo, Paolo %A Peto, Julian %A Pharoah, Paul D P %A Postma, Dirkje S %A Pouta, Anneli %A Pylkäs, Katri %A Radice, Paolo %A Ring, Susan %A Rivadeneira, Fernando %A Robino, Antonietta %A Rose, Lynda M %A Rudolph, Anja %A Salomaa, Veikko %A Sanna, Serena %A Schlessinger, David %A Schmidt, Marjanka K %A Southey, Mellissa C %A Sovio, Ulla %A Stampfer, Meir J %A Stöckl, Doris %A Storniolo, Anna M %A Timpson, Nicholas J %A Tyrer, Jonathan %A Visser, Jenny A %A Vollenweider, Peter %A Völzke, Henry %A Waeber, Gerard %A Waldenberger, Melanie %A Wallaschofski, Henri %A Wang, Qin %A Willemsen, Gonneke %A Winqvist, Robert %A Wolffenbuttel, Bruce H R %A Wright, Margaret J %A Boomsma, Dorret I %A Econs, Michael J %A Khaw, Kay-Tee %A Loos, Ruth J F %A McCarthy, Mark I %A Montgomery, Grant W %A Rice, John P %A Streeten, Elizabeth A %A Thorsteinsdottir, Unnur %A van Duijn, Cornelia M %A Alizadeh, Behrooz Z %A Bergmann, Sven %A Boerwinkle, Eric %A Boyd, Heather A %A Crisponi, Laura %A Gasparini, Paolo %A Gieger, Christian %A Harris, Tamara B %A Ingelsson, Erik %A Järvelin, Marjo-Riitta %A Kraft, Peter %A Lawlor, Debbie %A Metspalu, Andres %A Pennell, Craig E %A Ridker, Paul M %A Snieder, Harold %A Sørensen, Thorkild I A %A Spector, Tim D %A Strachan, David P %A Uitterlinden, André G %A Wareham, Nicholas J %A Widen, Elisabeth %A Zygmunt, Marek %A Murray, Anna %A Easton, Douglas F %A Stefansson, Kari %A Murabito, Joanne M %A Ong, Ken K %K Adolescent %K Age Factors %K Alleles %K Body Mass Index %K Breast Neoplasms %K Cardiovascular Diseases %K Child %K Diabetes Mellitus, Type 2 %K Europe %K Female %K Genetic Loci %K Genome-Wide Association Study %K Genomic Imprinting %K Humans %K Hypothalamo-Hypophyseal System %K Intercellular Signaling Peptides and Proteins %K Male %K Membrane Proteins %K Menarche %K Obesity %K Ovary %K Parents %K Polymorphism, Single Nucleotide %K Potassium Channels, Tandem Pore Domain %K Proteins %K Quantitative Trait Loci %K Receptors, GABA-B %K Receptors, Retinoic Acid %K Ribonucleoproteins %X

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

%B Nature %V 514 %P 92-7 %8 2014 Oct 2 %G eng %N 7520 %1 http://www.ncbi.nlm.nih.gov/pubmed/25231870?dopt=Abstract %R 10.1038/nature13545 %0 Journal Article %J Ophthalmic Genet %D 2013 %T A novel CRYBB2 missense mutation causing congenital autosomal dominant cataract in an Italian family. %A Faletra, Flavio %A d'Adamo, Adamo Pio %A Pensiero, Stefano %A Athanasakis, Emmanouil %A Catalano, Dario %A Bruno, Irene %A Gasparini, Paolo %K Amino Acid Sequence %K beta-Crystallin B Chain %K Cataract %K DNA Mutational Analysis %K Female %K Genes, Dominant %K Genetic Linkage %K Genotype %K Humans %K Italy %K Male %K Molecular Sequence Data %K Mutation, Missense %K Pedigree %K Phenotype %X

Congenital cataract is a leading cause of visual impairment in children and brings approximately 10% of childhood blindness worldwide. Molecular analysis revealed ~60 loci to be associated with several phenotypes of childhood cataracts. Until now, more than 30 loci and 18 genes on different chromosomes have been associated with autosomal dominant congenital cataract (ADCC). Here, we present a three-generation Italian family with a non syndromic ADCC. A linkage analysis carried out using HumanCytoSNP-12 DNA Analysis BeadChip led us to identify ten genomic regions virtually involved in the disease. All the genes located in these regions were scored for possible relationship with ADCC and, according to a strict clinical and genetic selection, 4 genes have been analyzed. A novel sequence variant was found in the CRYBB2 gene (p.Ser143Phe). This variant affects a conserved aminoacid in the third Greek key motif of the protein, cosegregates with the disease phenotype in all affected individuals and is not present both in the unaffected family members and 100 healthy control subjects. Finally, we identified the first CRYBB2 mutation in an Italian family causing a clinical picture of ADCC.

%B Ophthalmic Genet %V 34 %P 115-7 %8 2013 Mar-Jun %G eng %N 1-2 %1 http://www.ncbi.nlm.nih.gov/pubmed/22846113?dopt=Abstract %R 10.3109/13816810.2012.707273 %0 Journal Article %J Am J Med Genet A %D 2012 %T Does the 1.5 Mb microduplication in chromosome band Xp22.31 have a pathogenetic role? New contribution and a review of the literature. %A Faletra, Flavio %A d'Adamo, Adamo Pio %A Santa Rocca, Maria %A Carrozzi, Marco %A Perrone, Maria Dolores %A Pecile, Vanna %A Gasparini, Paolo %K Chromosome Breakpoints %K Chromosome Duplication %K Chromosomes, Human, X %K Hand Deformities, Congenital %K Humans %K Intellectual Disability %K Karyotyping %K Muscle Hypotonia %K Polymorphism, Single Nucleotide %K Protein Tyrosine Phosphatases %B Am J Med Genet A %V 158A %P 461-4 %8 2012 Feb %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/22140086?dopt=Abstract %R 10.1002/ajmg.a.34398 %0 Journal Article %J Nat Genet %D 2011 %T Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. %A Wain, Louise V %A Verwoert, Germaine C %A O'Reilly, Paul F %A Shi, Gang %A Johnson, Toby %A Johnson, Andrew D %A Bochud, Murielle %A Rice, Kenneth M %A Henneman, Peter %A Smith, Albert V %A Ehret, Georg B %A Amin, Najaf %A Larson, Martin G %A Mooser, Vincent %A Hadley, David %A Dörr, Marcus %A Bis, Joshua C %A Aspelund, Thor %A Esko, Tõnu %A Janssens, A Cecile J W %A Zhao, Jing Hua %A Heath, Simon %A Laan, Maris %A Fu, Jingyuan %A Pistis, Giorgio %A Luan, Jian'an %A Arora, Pankaj %A Lucas, Gavin %A Pirastu, Nicola %A Pichler, Irene %A Jackson, Anne U %A Webster, Rebecca J %A Zhang, Feng %A Peden, John F %A Schmidt, Helena %A Tanaka, Toshiko %A Campbell, Harry %A Igl, Wilmar %A Milaneschi, Yuri %A Hottenga, Jouke-Jan %A Vitart, Veronique %A Chasman, Daniel I %A Trompet, Stella %A Bragg-Gresham, Jennifer L %A Alizadeh, Behrooz Z %A Chambers, John C %A Guo, Xiuqing %A Lehtimäki, Terho %A Kuhnel, Brigitte %A Lopez, Lorna M %A Polasek, Ozren %A Boban, Mladen %A Nelson, Christopher P %A Morrison, Alanna C %A Pihur, Vasyl %A Ganesh, Santhi K %A Hofman, Albert %A Kundu, Suman %A Mattace-Raso, Francesco U S %A Rivadeneira, Fernando %A Sijbrands, Eric J G %A Uitterlinden, André G %A Hwang, Shih-Jen %A Vasan, Ramachandran S %A Wang, Thomas J %A Bergmann, Sven %A Vollenweider, Peter %A Waeber, Gerard %A Laitinen, Jaana %A Pouta, Anneli %A Zitting, Paavo %A McArdle, Wendy L %A Kroemer, Heyo K %A Völker, Uwe %A Völzke, Henry %A Glazer, Nicole L %A Taylor, Kent D %A Harris, Tamara B %A Alavere, Helene %A Haller, Toomas %A Keis, Aime %A Tammesoo, Mari-Liis %A Aulchenko, Yurii %A Barroso, Inês %A Khaw, Kay-Tee %A Galan, Pilar %A Hercberg, Serge %A Lathrop, Mark %A Eyheramendy, Susana %A Org, Elin %A Sõber, Siim %A Lu, Xiaowen %A Nolte, Ilja M %A Penninx, Brenda W %A Corre, Tanguy %A Masciullo, Corrado %A Sala, Cinzia %A Groop, Leif %A Voight, Benjamin F %A Melander, Olle %A O'Donnell, Christopher J %A Salomaa, Veikko %A d'Adamo, Adamo Pio %A Fabretto, Antonella %A Faletra, Flavio %A Ulivi, Sheila %A Del Greco, Fabiola M %A Facheris, Maurizio %A Collins, Francis S %A Bergman, Richard N %A Beilby, John P %A Hung, Joseph %A Musk, A William %A Mangino, Massimo %A Shin, So-Youn %A Soranzo, Nicole %A Watkins, Hugh %A Goel, Anuj %A Hamsten, Anders %A Gider, Pierre %A Loitfelder, Marisa %A Zeginigg, Marion %A Hernandez, Dena %A Najjar, Samer S %A Navarro, Pau %A Wild, Sarah H %A Corsi, Anna Maria %A Singleton, Andrew %A de Geus, Eco J C %A Willemsen, Gonneke %A Parker, Alex N %A Rose, Lynda M %A Buckley, Brendan %A Stott, David %A Orru, Marco %A Uda, Manuela %A van der Klauw, Melanie M %A Zhang, Weihua %A Li, Xinzhong %A Scott, James %A Chen, Yii-Der Ida %A Burke, Gregory L %A Kähönen, Mika %A Viikari, Jorma %A Döring, Angela %A Meitinger, Thomas %A Davies, Gail %A Starr, John M %A Emilsson, Valur %A Plump, Andrew %A Lindeman, Jan H %A Hoen, Peter A C 't %A König, Inke R %A Felix, Janine F %A Clarke, Robert %A Hopewell, Jemma C %A Ongen, Halit %A Breteler, Monique %A Debette, Stéphanie %A Destefano, Anita L %A Fornage, Myriam %A Mitchell, Gary F %A Smith, Nicholas L %A Holm, Hilma %A Stefansson, Kari %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Samani, Nilesh J %A Preuss, Michael %A Rudan, Igor %A Hayward, Caroline %A Deary, Ian J %A Wichmann, H-Erich %A Raitakari, Olli T %A Palmas, Walter %A Kooner, Jaspal S %A Stolk, Ronald P %A Jukema, J Wouter %A Wright, Alan F %A Boomsma, Dorret I %A Bandinelli, Stefania %A Gyllensten, Ulf B %A Wilson, James F %A Ferrucci, Luigi %A Schmidt, Reinhold %A Farrall, Martin %A Spector, Tim D %A Palmer, Lyle J %A Tuomilehto, Jaakko %A Pfeufer, Arne %A Gasparini, Paolo %A Siscovick, David %A Altshuler, David %A Loos, Ruth J F %A Toniolo, Daniela %A Snieder, Harold %A Gieger, Christian %A Meneton, Pierre %A Wareham, Nicholas J %A Oostra, Ben A %A Metspalu, Andres %A Launer, Lenore %A Rettig, Rainer %A Strachan, David P %A Beckmann, Jacques S %A Witteman, Jacqueline C M %A Erdmann, Jeanette %A van Dijk, Ko Willems %A Boerwinkle, Eric %A Boehnke, Michael %A Ridker, Paul M %A Järvelin, Marjo-Riitta %A Chakravarti, Aravinda %A Abecasis, Goncalo R %A Gudnason, Vilmundur %A Newton-Cheh, Christopher %A Levy, Daniel %A Munroe, Patricia B %A Psaty, Bruce M %A Caulfield, Mark J %A Rao, Dabeeru C %A Tobin, Martin D %A Elliott, Paul %A van Duijn, Cornelia M %K Arteries %K Blood Pressure %K Case-Control Studies %K Follow-Up Studies %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Hypertension %K Linkage Disequilibrium %K Polymorphism, Single Nucleotide %X

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

%B Nat Genet %V 43 %P 1005-11 %8 2011 Oct %G eng %N 10 %1 http://www.ncbi.nlm.nih.gov/pubmed/21909110?dopt=Abstract %R 10.1038/ng.922