@article {10427, title = {A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.}, journal = {Am J Hum Genet}, volume = {102}, year = {2018}, month = {2018 03 01}, pages = {375-400}, abstract = {

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined \~{}18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5~{\texttimes} 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5~{\texttimes} 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

}, keywords = {Blood Pressure, Cohort Studies, Continental Population Groups, Diastole, Epistasis, Genetic, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Smoking, Systole}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2018.01.015}, author = {Sung, Yun J and Winkler, Thomas W and de Las Fuentes, Lisa and Bentley, Amy R and Brown, Michael R and Kraja, Aldi T and Schwander, Karen and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Lu, Yingchang and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Feitosa, Mary F and Kilpel{\"a}inen, Tuomas O and Richard, Melissa A and Noordam, Raymond and Aslibekyan, Stella and Aschard, Hugues and Bartz, Traci M and Dorajoo, Rajkumar and Liu, Yongmei and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert Vernon and Tajuddin, Salman M and Tayo, Bamidele O and Warren, Helen R and Zhao, Wei and Zhou, Yanhua and Matoba, Nana and Sofer, Tamar and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gandin, Ilaria and Gao, Chuan and Giulianini, Franco and Goel, Anuj and Harris, Sarah E and Hartwig, Fernando Pires and Horimoto, Andrea R V R and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and Kuhnel, Brigitte and Leander, Karin and Lee, Wen-Jane and Lin, Keng-Hung and {\textquoteright}an Luan, Jian and McKenzie, Colin A and Meian, He and Nelson, Christopher P and Rauramaa, Rainer and Schupf, Nicole and Scott, Robert A and Sheu, Wayne H H and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Wang, Heming and Wang, Yajuan and Ware, Erin B and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Alfred, Tamuno and Amin, Najaf and Arking, Dan and Aung, Tin and Barr, R Graham and Bielak, Lawrence F and Boerwinkle, Eric and Bottinger, Erwin P and Braund, Peter S and Brody, Jennifer A and Broeckel, Ulrich and Cabrera, Claudia P and Cade, Brian and Caizheng, Yu and Campbell, Archie and Canouil, Micka{\"e}l and Chakravarti, Aravinda and Chauhan, Ganesh and Christensen, Kaare and Cocca, Massimiliano and Collins, Francis S and Connell, John M and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Debette, St{\'e}phanie and D{\"o}rr, Marcus and Duan, Qing and Eaton, Charles B and Ehret, Georg and Evangelou, Evangelos and Faul, Jessica D and Fisher, Virginia A and Forouhi, Nita G and Franco, Oscar H and Friedlander, Yechiel and Gao, He and Gigante, Bruna and Graff, Misa and Gu, C Charles and Gu, Dongfeng and Gupta, Preeti and Hagenaars, Saskia P and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Hofman, Albert and Howard, Barbara V and Hunt, Steven and Irvin, Marguerite R and Jia, Yucheng and Joehanes, Roby and Justice, Anne E and Katsuya, Tomohiro and Kaufman, Joel and Kerrison, Nicola D and Khor, Chiea Chuen and Koh, Woon-Puay and Koistinen, Heikki A and Komulainen, Pirjo and Kooperberg, Charles and Krieger, Jose E and Kubo, Michiaki and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Lim, Sing Hui and Lin, Shiow and Liu, Ching-Ti and Liu, Jianjun and Liu, Jingmin and Liu, Kiang and Liu, Yeheng and Loh, Marie and Lohman, Kurt K and Long, Jirong and Louie, Tin and M{\"a}gi, Reedik and Mahajan, Anubha and Meitinger, Thomas and Metspalu, Andres and Milani, Lili and Momozawa, Yukihide and Morris, Andrew P and Mosley, Thomas H and Munson, Peter and Murray, Alison D and Nalls, Mike A and Nasri, Ubaydah and Norris, Jill M and North, Kari and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Palmer, Nicholette D and Pankow, James S and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Raitakari, Olli T and Renstrom, Frida and Rice, Treva K and Ridker, Paul M and Robino, Antonietta and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Sabanayagam, Charumathi and Salako, Babatunde L and Sandow, Kevin and Schmidt, Carsten O and Schreiner, Pamela J and Scott, William R and Seshadri, Sudha and Sever, Peter and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Uitterlinden, Andr{\'e} G and Waldenberger, Melanie and Wang, Lihua and Wang, Ya X and Wei, Wen Bin and Williams, Christine and Wilson, Gregory and Wojczynski, Mary K and Yao, Jie and Yuan, Jian-Min and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Chen, Yii-Der Ida and de Faire, Ulf and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Forrester, Terrence and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Horta, Bernardo Lessa and Hung, Yi-Jen and Jonas, Jost B and Kato, Norihiro and Kooner, Jaspal S and Laakso, Markku and Lehtim{\"a}ki, Terho and Liang, Kae-Woei and Magnusson, Patrik K E and Newman, Anne B and Oldehinkel, Albertine J and Pereira, Alexandre C and Redline, Susan and Rettig, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Kamatani, Yoichiro and Laurie, Cathy C and Bouchard, Claude and Cooper, Richard S and Evans, Michele K and Gudnason, Vilmundur and Kardia, Sharon L R and Kritchevsky, Stephen B and Levy, Daniel and O{\textquoteright}Connell, Jeff R and Psaty, Bruce M and van Dam, Rob M and Sims, Mario and Arnett, Donna K and Mook-Kanamori, Dennis O and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and Fornage, Myriam and Rotimi, Charles N and Province, Michael A and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Loos, Ruth J F and Reiner, Alex P and Rotter, Jerome I and Zhu, Xiaofeng and Bierut, Laura J and Gauderman, W James and Caulfield, Mark J and Elliott, Paul and Rice, Kenneth and Munroe, Patricia B and Morrison, Alanna C and Cupples, L Adrienne and Rao, Dabeeru C and Chasman, Daniel I} } @article {10823, title = {Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0198166}, abstract = {

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Alcohol Drinking, Blood Pressure, Cohort Studies, Continental Population Groups, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0198166}, author = {Feitosa, Mary F and Kraja, Aldi T and Chasman, Daniel I and Sung, Yun J and Winkler, Thomas W and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Bentley, Amy R and Brown, Michael R and Schwander, Karen and Richard, Melissa A and Noordam, Raymond and Aschard, Hugues and Bartz, Traci M and Bielak, Lawrence F and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P and Horimoto, Andrea R V R and Lohman, Kurt K and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert V and Tajuddin, Salman M and Wojczynski, Mary K and Alver, Maris and Boissel, Mathilde and Cai, Qiuyin and Campbell, Archie and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gao, Chuan and Goel, Anuj and Hagemeijer, Yanick and Harris, Sarah E and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and Komulainen, Pirjo and Kuhnel, Brigitte and Laguzzi, Federica and Luan, Jian{\textquoteright}an and Matoba, Nana and Nolte, Ilja M and Padmanabhan, Sandosh and Riaz, Muhammad and Rueedi, Rico and Robino, Antonietta and Said, M Abdullah and Scott, Robert A and Sofer, Tamar and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and Tayo, Bamidele O and van der Most, Peter J and Varga, Tibor V and Vitart, Veronique and Wang, Yajuan and Ware, Erin B and Warren, Helen R and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Amin, Najaf and Amini, Marzyeh and Arking, Dan E and Aung, Tin and Boerwinkle, Eric and Borecki, Ingrid and Broeckel, Ulrich and Brown, Morris and Brumat, Marco and Burke, Gregory L and Canouil, Micka{\"e}l and Chakravarti, Aravinda and Charumathi, Sabanayagam and Ida Chen, Yii-Der and Connell, John M and Correa, Adolfo and de Las Fuentes, Lisa and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Deng, Xuan and Ding, Jingzhong and Duan, Qing and Eaton, Charles B and Ehret, Georg and Eppinga, Ruben N and Evangelou, Evangelos and Faul, Jessica D and Felix, Stephan B and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Friedlander, Yechiel and Gandin, Ilaria and Gao, He and Ghanbari, Mohsen and Gigante, Bruna and Gu, C Charles and Gu, Dongfeng and Hagenaars, Saskia P and Hallmans, Goran and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Howard, Barbara V and Ikram, M Arfan and John, Ulrich and Katsuya, Tomohiro and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Krieger, Jose E and Kritchevsky, Stephen B and Kubo, Michiaki and Kuusisto, Johanna and Lakka, Timo A and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Lin, Shiow and Liu, Jianjun and Liu, Jingmin and Loh, Marie and Louie, Tin and M{\"a}gi, Reedik and McKenzie, Colin A and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Milani, Lili and Mohlke, Karen L and Momozawa, Yukihide and Nalls, Mike A and Nelson, Christopher P and Sotoodehnia, Nona and Norris, Jill M and O{\textquoteright}Connell, Jeff R and Palmer, Nicholette D and Perls, Thomas and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Poulter, Neil and Raffel, Leslie J and Raitakari, Olli T and Roll, Kathryn and Rose, Lynda M and Rosendaal, Frits R and Rotter, Jerome I and Schmidt, Carsten O and Schreiner, Pamela J and Schupf, Nicole and Scott, William R and Sever, Peter S and Shi, Yuan and Sidney, Stephen and Sims, Mario and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Stringham, Heather M and Tan, Nicholas Y Q and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Turner, Stephen T and Uitterlinden, Andr{\'e} G and Vollenweider, Peter and Waldenberger, Melanie and Wang, Lihua and Wang, Ya Xing and Wei, Wen Bin and Williams, Christine and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Jonas, Jost Bruno and Kamatani, Yoichiro and Kato, Norihiro and Kooner, Jaspal S and Kutalik, Zolt{\'a}n and Laakso, Markku and Laurie, Cathy C and Leander, Karin and Lehtim{\"a}ki, Terho and Study, Lifelines Cohort and Magnusson, Patrik K E and Oldehinkel, Albertine J and Penninx, Brenda W J H and Polasek, Ozren and Porteous, David J and Rauramaa, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Bouchard, Claude and Christensen, Kaare and Evans, Michele K and Gudnason, Vilmundur and Horta, Bernardo L and Kardia, Sharon L R and Liu, Yongmei and Pereira, Alexandre C and Psaty, Bruce M and Ridker, Paul M and van Dam, Rob M and Gauderman, W James and Zhu, Xiaofeng and Mook-Kanamori, Dennis O and Fornage, Myriam and Rotimi, Charles N and Cupples, L Adrienne and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Kooperberg, Charles and Palmas, Walter and Rice, Kenneth and Morrison, Alanna C and Elliott, Paul and Caulfield, Mark J and Munroe, Patricia B and Rao, Dabeeru C and Province, Michael A and Levy, Daniel} } @article {10572, title = { and Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.}, journal = {J Am Soc Nephrol}, volume = {28}, year = {2017}, month = {2017 Mar}, pages = {981-994}, abstract = {

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (: 111,666; : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (, , and ; <3.7{\texttimes}10), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, (=5.4{\texttimes}10 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of and -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

}, keywords = {Animals, Exome, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Son of Sevenless Proteins, Zebrafish}, issn = {1533-3450}, doi = {10.1681/ASN.2016020131}, author = {Li, Man and Li, Yong and Weeks, Olivia and Mijatovic, Vladan and Teumer, Alexander and Huffman, Jennifer E and Tromp, Gerard and Fuchsberger, Christian and Gorski, Mathias and Lyytik{\"a}inen, Leo-Pekka and Nutile, Teresa and Sedaghat, Sanaz and Sorice, Rossella and Tin, Adrienne and Yang, Qiong and Ahluwalia, Tarunveer S and Arking, Dan E and Bihlmeyer, Nathan A and B{\"o}ger, Carsten A and Carroll, Robert J and Chasman, Daniel I and Cornelis, Marilyn C and Dehghan, Abbas and Faul, Jessica D and Feitosa, Mary F and Gambaro, Giovanni and Gasparini, Paolo and Giulianini, Franco and Heid, Iris and Huang, Jinyan and Imboden, Medea and Jackson, Anne U and Jeff, Janina and Jhun, Min A and Katz, Ronit and Kifley, Annette and Kilpel{\"a}inen, Tuomas O and Kumar, Ashish and Laakso, Markku and Li-Gao, Ruifang and Lohman, Kurt and Lu, Yingchang and M{\"a}gi, Reedik and Malerba, Giovanni and Mihailov, Evelin and Mohlke, Karen L and Mook-Kanamori, Dennis O and Robino, Antonietta and Ruderfer, Douglas and Salvi, Erika and Schick, Ursula M and Schulz, Christina-Alexandra and Smith, Albert V and Smith, Jennifer A and Traglia, Michela and Yerges-Armstrong, Laura M and Zhao, Wei and Goodarzi, Mark O and Kraja, Aldi T and Liu, Chunyu and Wessel, Jennifer and Boerwinkle, Eric and Borecki, Ingrid B and Bork-Jensen, Jette and Bottinger, Erwin P and Braga, Daniele and Brandslund, Ivan and Brody, Jennifer A and Campbell, Archie and Carey, David J and Christensen, Cramer and Coresh, Josef and Crook, Errol and Curhan, Gary C and Cusi, Daniele and de Boer, Ian H and de Vries, Aiko P J and Denny, Joshua C and Devuyst, Olivier and Dreisbach, Albert W and Endlich, Karlhans and Esko, T{\~o}nu and Franco, Oscar H and Fulop, Tibor and Gerhard, Glenn S and Gl{\"u}mer, Charlotte and Gottesman, Omri and Grarup, Niels and Gudnason, Vilmundur and Hansen, Torben and Harris, Tamara B and Hayward, Caroline and Hocking, Lynne and Hofman, Albert and Hu, Frank B and Husemoen, Lise Lotte N and Jackson, Rebecca D and J{\o}rgensen, Torben and J{\o}rgensen, Marit E and K{\"a}h{\"o}nen, Mika and Kardia, Sharon L R and K{\"o}nig, Wolfgang and Kooperberg, Charles and Kriebel, Jennifer and Launer, Lenore J and Lauritzen, Torsten and Lehtim{\"a}ki, Terho and Levy, Daniel and Linksted, Pamela and Linneberg, Allan and Liu, Yongmei and Loos, Ruth J F and Lupo, Antonio and Meisinger, Christine and Melander, Olle and Metspalu, Andres and Mitchell, Paul and Nauck, Matthias and N{\"u}rnberg, Peter and Orho-Melander, Marju and Parsa, Afshin and Pedersen, Oluf and Peters, Annette and Peters, Ulrike and Polasek, Ozren and Porteous, David and Probst-Hensch, Nicole M and Psaty, Bruce M and Qi, Lu and Raitakari, Olli T and Reiner, Alex P and Rettig, Rainer and Ridker, Paul M and Rivadeneira, Fernando and Rossouw, Jacques E and Schmidt, Frank and Siscovick, David and Soranzo, Nicole and Strauch, Konstantin and Toniolo, Daniela and Turner, Stephen T and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and Velayutham, Dinesh and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Waldenberger, Melanie and Wang, Jie Jin and Weir, David R and Witte, Daniel and Kuivaniemi, Helena and Fox, Caroline S and Franceschini, Nora and Goessling, Wolfram and K{\"o}ttgen, Anna and Chu, Audrey Y} } @article {10556, title = {Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.}, journal = {Nat Genet}, volume = {49}, year = {2017}, month = {2017 Jun}, pages = {834-841}, abstract = {

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to \~{}370,000 women, we identify 389 independent signals (P < 5 {\texttimes} 10) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain \~{}7.4\% of the population variance in age at menarche, corresponding to \~{}25\% of the estimated heritability. We implicate \~{}250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

}, keywords = {Adolescent, Age Factors, Body Mass Index, Databases, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomic Imprinting, Humans, Intercellular Signaling Peptides and Proteins, Male, Membrane Proteins, Menarche, Neoplasms, Polymorphism, Single Nucleotide, Puberty, Quantitative Trait Loci, Ribonucleoproteins, Risk Factors}, issn = {1546-1718}, doi = {10.1038/ng.3841}, author = {Day, Felix R and Thompson, Deborah J and Helgason, Hannes and Chasman, Daniel I and Finucane, Hilary and Sulem, Patrick and Ruth, Katherine S and Whalen, Sean and Sarkar, Abhishek K and Albrecht, Eva and Altmaier, Elisabeth and Amini, Marzyeh and Barbieri, Caterina M and Boutin, Thibaud and Campbell, Archie and Demerath, Ellen and Giri, Ayush and He, Chunyan and Hottenga, Jouke J and Karlsson, Robert and Kolcic, Ivana and Loh, Po-Ru and Lunetta, Kathryn L and Mangino, Massimo and Marco, Brumat and McMahon, George and Medland, Sarah E and Nolte, Ilja M and Noordam, Raymond and Nutile, Teresa and Paternoster, Lavinia and Perjakova, Natalia and Porcu, Eleonora and Rose, Lynda M and Schraut, Katharina E and Segr{\`e}, Ayellet V and Smith, Albert V and Stolk, Lisette and Teumer, Alexander and Andrulis, Irene L and Bandinelli, Stefania and Beckmann, Matthias W and Benitez, Javier and Bergmann, Sven and Bochud, Murielle and Boerwinkle, Eric and Bojesen, Stig E and Bolla, Manjeet K and Brand, Judith S and Brauch, Hiltrud and Brenner, Hermann and Broer, Linda and Br{\"u}ning, Thomas and Buring, Julie E and Campbell, Harry and Catamo, Eulalia and Chanock, Stephen and Chenevix-Trench, Georgia and Corre, Tanguy and Couch, Fergus J and Cousminer, Diana L and Cox, Angela and Crisponi, Laura and Czene, Kamila and Davey Smith, George and de Geus, Eco J C N and de Mutsert, Ren{\'e}e and De Vivo, Immaculata and Dennis, Joe and Devilee, Peter and Dos-Santos-Silva, Isabel and Dunning, Alison M and Eriksson, Johan G and Fasching, Peter A and Fern{\'a}ndez-Rhodes, Lindsay and Ferrucci, Luigi and Flesch-Janys, Dieter and Franke, Lude and Gabrielson, Marike and Gandin, Ilaria and Giles, Graham G and Grallert, Harald and Gudbjartsson, Daniel F and Guenel, Pascal and Hall, Per and Hallberg, Emily and Hamann, Ute and Harris, Tamara B and Hartman, Catharina A and Heiss, Gerardo and Hooning, Maartje J and Hopper, John L and Hu, Frank and Hunter, David J and Ikram, M Arfan and Im, Hae Kyung and J{\"a}rvelin, Marjo-Riitta and Joshi, Peter K and Karasik, David and Kellis, Manolis and Kutalik, Zolt{\'a}n and LaChance, Genevieve and Lambrechts, Diether and Langenberg, Claudia and Launer, Lenore J and Laven, Joop S E and Lenarduzzi, Stefania and Li, Jingmei and Lind, Penelope A and Lindstr{\"o}m, Sara and Liu, Yongmei and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Mannermaa, Arto and Mbarek, Hamdi and McCarthy, Mark I and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Metspalu, Andres and Michailidou, Kyriaki and Milani, Lili and Milne, Roger L and Montgomery, Grant W and Mulligan, Anna M and Nalls, Mike A and Navarro, Pau and Nevanlinna, Heli and Nyholt, Dale R and Oldehinkel, Albertine J and O{\textquoteright}Mara, Tracy A and Padmanabhan, Sandosh and Palotie, Aarno and Pedersen, Nancy and Peters, Annette and Peto, Julian and Pharoah, Paul D P and Pouta, Anneli and Radice, Paolo and Rahman, Iffat and Ring, Susan M and Robino, Antonietta and Rosendaal, Frits R and Rudan, Igor and Rueedi, Rico and Ruggiero, Daniela and Sala, Cinzia F and Schmidt, Marjanka K and Scott, Robert A and Shah, Mitul and Sorice, Rossella and Southey, Melissa C and Sovio, Ulla and Stampfer, Meir and Steri, Maristella and Strauch, Konstantin and Tanaka, Toshiko and Tikkanen, Emmi and Timpson, Nicholas J and Traglia, Michela and Truong, Therese and Tyrer, Jonathan P and Uitterlinden, Andr{\'e} G and Edwards, Digna R Velez and Vitart, Veronique and V{\"o}lker, Uwe and Vollenweider, Peter and Wang, Qin and Widen, Elisabeth and van Dijk, Ko Willems and Willemsen, Gonneke and Winqvist, Robert and Wolffenbuttel, Bruce H R and Zhao, Jing Hua and Zoledziewska, Magdalena and Zygmunt, Marek and Alizadeh, Behrooz Z and Boomsma, Dorret I and Ciullo, Marina and Cucca, Francesco and Esko, T{\~o}nu and Franceschini, Nora and Gieger, Christian and Gudnason, Vilmundur and Hayward, Caroline and Kraft, Peter and Lawlor, Debbie A and Magnusson, Patrik K E and Martin, Nicholas G and Mook-Kanamori, Dennis O and Nohr, Ellen A and Polasek, Ozren and Porteous, David and Price, Alkes L and Ridker, Paul M and Snieder, Harold and Spector, Tim D and St{\"o}ckl, Doris and Toniolo, Daniela and Ulivi, Sheila and Visser, Jenny A and V{\"o}lzke, Henry and Wareham, Nicholas J and Wilson, James F and Spurdle, Amanda B and Thorsteindottir, Unnur and Pollard, Katherine S and Easton, Douglas F and Tung, Joyce Y and Chang-Claude, Jenny and Hinds, David and Murray, Anna and Murabito, Joanne M and Stefansson, Kari and Ong, Ken K and Perry, John R B} } @article {7696, title = {Directional dominance on stature and cognition in~diverse human populations.}, journal = {Nature}, volume = {523}, year = {2015}, month = {2015 Jul 23}, pages = {459-62}, abstract = {

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs~of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 {\texttimes} 10(-300), 2.1 {\texttimes} 10(-6), 2.5 {\texttimes} 10(-10) and 1.8 {\texttimes} 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months{\textquoteright} less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

}, keywords = {Biological Evolution, Blood Pressure, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype}, issn = {1476-4687}, doi = {10.1038/nature14618}, author = {Joshi, Peter K and Esko, T{\~o}nu and Mattsson, Hannele and Eklund, Niina and Gandin, Ilaria and Nutile, Teresa and Jackson, Anne U and Schurmann, Claudia and Smith, Albert V and Zhang, Weihua and Okada, Yukinori and Stan{\v c}{\'a}kov{\'a}, Alena and Faul, Jessica D and Zhao, Wei and Bartz, Traci M and Concas, Maria Pina and Franceschini, Nora and Enroth, Stefan and Vitart, Veronique and Trompet, Stella and Guo, Xiuqing and Chasman, Daniel I and O{\textquoteright}Connel, Jeffrey R and Corre, Tanguy and Nongmaithem, Suraj S and Chen, Yuning and Mangino, Massimo and Ruggiero, Daniela and Traglia, Michela and Farmaki, Aliki-Eleni and Kacprowski, Tim and Bjonnes, Andrew and van der Spek, Ashley and Wu, Ying and Giri, Anil K and Yanek, Lisa R and Wang, Lihua and Hofer, Edith and Rietveld, Cornelius A and McLeod, Olga and Cornelis, Marilyn C and Pattaro, Cristian and Verweij, Niek and Baumbach, Clemens and Abdellaoui, Abdel and Warren, Helen R and Vuckovic, Dragana and Mei, Hao and Bouchard, Claude and Perry, John R B and Cappellani, Stefania and Mirza, Saira S and Benton, Miles C and Broeckel, Ulrich and Medland, Sarah E and Lind, Penelope A and Malerba, Giovanni and Drong, Alexander and Yengo, Loic and Bielak, Lawrence F and Zhi, Degui and van der Most, Peter J and Shriner, Daniel and M{\"a}gi, Reedik and Hemani, Gibran and Karaderi, Tugce and Wang, Zhaoming and Liu, Tian and Demuth, Ilja and Zhao, Jing Hua and Meng, Weihua and Lataniotis, Lazaros and van der Laan, Sander W and Bradfield, Jonathan P and Wood, Andrew R and Bonnefond, Amelie and Ahluwalia, Tarunveer S and Hall, Leanne M and Salvi, Erika and Yazar, Seyhan and Carstensen, Lisbeth and de Haan, Hugoline G and Abney, Mark and Afzal, Uzma and Allison, Matthew A and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Barr, R Graham and Baumeister, Sebastian E and Benjamin, Daniel J and Bergmann, Sven and Boerwinkle, Eric and Bottinger, Erwin P and Campbell, Archie and Chakravarti, Aravinda and Chan, Yingleong and Chanock, Stephen J and Chen, Constance and Chen, Y-D Ida and Collins, Francis S and Connell, John and Correa, Adolfo and Cupples, L Adrienne and Smith, George Davey and Davies, Gail and D{\"o}rr, Marcus and Ehret, Georg and Ellis, Stephen B and Feenstra, Bjarke and Feitosa, Mary F and Ford, Ian and Fox, Caroline S and Frayling, Timothy M and Friedrich, Nele and Geller, Frank and Scotland, Generation and Gillham-Nasenya, Irina and Gottesman, Omri and Graff, Misa and Grodstein, Francine and Gu, Charles and Haley, Chris and Hammond, Christopher J and Harris, Sarah E and Harris, Tamara B and Hastie, Nicholas D and Heard-Costa, Nancy L and Heikkil{\"a}, Kauko and Hocking, Lynne J and Homuth, Georg and Hottenga, Jouke-Jan and Huang, Jinyan and Huffman, Jennifer E and Hysi, Pirro G and Ikram, M Arfan and Ingelsson, Erik and Joensuu, Anni and Johansson, {\r A}sa and Jousilahti, Pekka and Jukema, J Wouter and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kanoni, Stavroula and Kerr, Shona M and Khan, Nazir M and Koellinger, Philipp and Koistinen, Heikki A and Kooner, Manraj K and Kubo, Michiaki and Kuusisto, Johanna and Lahti, Jari and Launer, Lenore J and Lea, Rodney A and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Liewald, David C M and Lind, Lars and Loh, Marie and Lokki, Marja-Liisa and London, Stephanie J and Loomis, Stephanie J and Loukola, Anu and Lu, Yingchang and Lumley, Thomas and Lundqvist, Annamari and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Masciullo, Corrado and Matchan, Angela and Mathias, Rasika A and Matsuda, Koichi and Meigs, James B and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Mentch, Frank D and Mihailov, Evelin and Milani, Lili and Montasser, May E and Montgomery, Grant W and Morrison, Alanna and Myers, Richard H and Nadukuru, Rajiv and Navarro, Pau and Nelis, Mari and Nieminen, Markku S and Nolte, Ilja M and O{\textquoteright}Connor, George T and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Pankow, James S and Patarcic, Inga and Pavani, Francesca and Peyser, Patricia A and Pietilainen, Kirsi and Poulter, Neil and Prokopenko, Inga and Ralhan, Sarju and Redmond, Paul and Rich, Stephen S and Rissanen, Harri and Robino, Antonietta and Rose, Lynda M and Rose, Richard and Sala, Cinzia and Salako, Babatunde and Salomaa, Veikko and Sarin, Antti-Pekka and Saxena, Richa and Schmidt, Helena and Scott, Laura J and Scott, William R and Sennblad, Bengt and Seshadri, Sudha and Sever, Peter and Shrestha, Smeeta and Smith, Blair H and Smith, Jennifer A and Soranzo, Nicole and Sotoodehnia, Nona and Southam, Lorraine and Stanton, Alice V and Stathopoulou, Maria G and Strauch, Konstantin and Strawbridge, Rona J and Suderman, Matthew J and Tandon, Nikhil and Tang, Sian-Tsun and Taylor, Kent D and Tayo, Bamidele O and T{\"o}glhofer, Anna Maria and Tomaszewski, Maciej and T{\v s}ernikova, Natalia and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and Vaidya, Dhananjay and van Hylckama Vlieg, Astrid and van Setten, Jessica and Vasankari, Tuula and Vedantam, Sailaja and Vlachopoulou, Efthymia and Vozzi, Diego and Vuoksimaa, Eero and Waldenberger, Melanie and Ware, Erin B and Wentworth-Shields, William and Whitfield, John B and Wild, Sarah and Willemsen, Gonneke and Yajnik, Chittaranjan S and Yao, Jie and Zaza, Gianluigi and Zhu, Xiaofeng and Salem, Rany M and Melbye, Mads and Bisgaard, Hans and Samani, Nilesh J and Cusi, Daniele and Mackey, David A and Cooper, Richard S and Froguel, Philippe and Pasterkamp, Gerard and Grant, Struan F A and Hakonarson, Hakon and Ferrucci, Luigi and Scott, Robert A and Morris, Andrew D and Palmer, Colin N A and Dedoussis, George and Deloukas, Panos and Bertram, Lars and Lindenberger, Ulman and Berndt, Sonja I and Lindgren, Cecilia M and Timpson, Nicholas J and T{\"o}njes, Anke and Munroe, Patricia B and S{\o}rensen, Thorkild I A and Rotimi, Charles N and Arnett, Donna K and Oldehinkel, Albertine J and Kardia, Sharon L R and Balkau, Beverley and Gambaro, Giovanni and Morris, Andrew P and Eriksson, Johan G and Wright, Margie J and Martin, Nicholas G and Hunt, Steven C and Starr, John M and Deary, Ian J and Griffiths, Lyn R and Tiemeier, Henning and Pirastu, Nicola and Kaprio, Jaakko and Wareham, Nicholas J and P{\'e}russe, Louis and Wilson, James G and Girotto, Giorgia and Caulfield, Mark J and Raitakari, Olli and Boomsma, Dorret I and Gieger, Christian and van der Harst, Pim and Hicks, Andrew A and Kraft, Peter and Sinisalo, Juha and Knekt, Paul and Johannesson, Magnus and Magnusson, Patrik K E and Hamsten, Anders and Schmidt, Reinhold and Borecki, Ingrid B and Vartiainen, Erkki and Becker, Diane M and Bharadwaj, Dwaipayan and Mohlke, Karen L and Boehnke, Michael and van Duijn, Cornelia M and Sanghera, Dharambir K and Teumer, Alexander and Zeggini, Eleftheria and Metspalu, Andres and Gasparini, Paolo and Ulivi, Sheila and Ober, Carole and Toniolo, Daniela and Rudan, Igor and Porteous, David J and Ciullo, Marina and Spector, Tim D and Hayward, Caroline and Dupuis, Jos{\'e}e and Loos, Ruth J F and Wright, Alan F and Chandak, Giriraj R and Vollenweider, Peter and Shuldiner, Alan R and Ridker, Paul M and Rotter, Jerome I and Sattar, Naveed and Gyllensten, Ulf and North, Kari E and Pirastu, Mario and Psaty, Bruce M and Weir, David R and Laakso, Markku and Gudnason, Vilmundur and Takahashi, Atsushi and Chambers, John C and Kooner, Jaspal S and Strachan, David P and Campbell, Harry and Hirschhorn, Joel N and Perola, Markus and Polasek, Ozren and Wilson, James F} } @article {8066, title = {Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.}, journal = {Nat Genet}, volume = {47}, year = {2015}, month = {2015 Nov}, pages = {1294-303}, abstract = {

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in \~{}70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (\~{}6\% increase in risk per year; P = 3 {\texttimes} 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

}, issn = {1546-1718}, doi = {10.1038/ng.3412}, author = {Day, Felix R and Ruth, Katherine S and Thompson, Deborah J and Lunetta, Kathryn L and Pervjakova, Natalia and Chasman, Daniel I and Stolk, Lisette and Finucane, Hilary K and Sulem, Patrick and Bulik-Sullivan, Brendan and Esko, T{\~o}nu and Johnson, Andrew D and Elks, Cathy E and Franceschini, Nora and He, Chunyan and Altmaier, Elisabeth and Brody, Jennifer A and Franke, Lude L and Huffman, Jennifer E and Keller, Margaux F and McArdle, Patrick F and Nutile, Teresa and Porcu, Eleonora and Robino, Antonietta and Rose, Lynda M and Schick, Ursula M and Smith, Jennifer A and Teumer, Alexander and Traglia, Michela and Vuckovic, Dragana and Yao, Jie and Zhao, Wei and Albrecht, Eva and Amin, Najaf and Corre, Tanguy and Hottenga, Jouke-Jan and Mangino, Massimo and Smith, Albert V and Tanaka, Toshiko and Abecasis, Goncalo R and Andrulis, Irene L and Anton-Culver, Hoda and Antoniou, Antonis C and Arndt, Volker and Arnold, Alice M and Barbieri, Caterina and Beckmann, Matthias W and Beeghly-Fadiel, Alicia and Benitez, Javier and Bernstein, Leslie and Bielinski, Suzette J and Blomqvist, Carl and Boerwinkle, Eric and Bogdanova, Natalia V and Bojesen, Stig E and Bolla, Manjeet K and Borresen-Dale, Anne-Lise and Boutin, Thibaud S and Brauch, Hiltrud and Brenner, Hermann and Br{\"u}ning, Thomas and Burwinkel, Barbara and Campbell, Archie and Campbell, Harry and Chanock, Stephen J and Chapman, J Ross and Chen, Yii-Der Ida and Chenevix-Trench, Georgia and Couch, Fergus J and Coviello, Andrea D and Cox, Angela and Czene, Kamila and Darabi, Hatef and De Vivo, Immaculata and Demerath, Ellen W and Dennis, Joe and Devilee, Peter and D{\"o}rk, Thilo and Dos-Santos-Silva, Isabel and Dunning, Alison M and Eicher, John D and Fasching, Peter A and Faul, Jessica D and Figueroa, Jonine and Flesch-Janys, Dieter and Gandin, Ilaria and Garcia, Melissa E and Garc{\'\i}a-Closas, Montserrat and Giles, Graham G and Girotto, Giorgia G and Goldberg, Mark S and Gonz{\'a}lez-Neira, Anna and Goodarzi, Mark O and Grove, Megan L and Gudbjartsson, Daniel F and Guenel, Pascal and Guo, Xiuqing and Haiman, Christopher A and Hall, Per and Hamann, Ute and Henderson, Brian E and Hocking, Lynne J and Hofman, Albert and Homuth, Georg and Hooning, Maartje J and Hopper, John L and Hu, Frank B and Huang, Jinyan and Humphreys, Keith and Hunter, David J and Jakubowska, Anna and Jones, Samuel E and Kabisch, Maria and Karasik, David and Knight, Julia A and Kolcic, Ivana and Kooperberg, Charles and Kosma, Veli-Matti and Kriebel, Jennifer and Kristensen, Vessela and Lambrechts, Diether and Langenberg, Claudia and Li, Jingmei and Li, Xin and Lindstr{\"o}m, Sara and Liu, Yongmei and Luan, Jian{\textquoteright}an and Lubinski, Jan and M{\"a}gi, Reedik and Mannermaa, Arto and Manz, Judith and Margolin, Sara and Marten, Jonathan and Martin, Nicholas G and Masciullo, Corrado and Meindl, Alfons and Michailidou, Kyriaki and Mihailov, Evelin and Milani, Lili and Milne, Roger L and M{\"u}ller-Nurasyid, Martina and Nalls, Michael and Neale, Benjamin M and Nevanlinna, Heli and Neven, Patrick and Newman, Anne B and Nordestgaard, B{\o}rge G and Olson, Janet E and Padmanabhan, Sandosh and Peterlongo, Paolo and Peters, Ulrike and Petersmann, Astrid and Peto, Julian and Pharoah, Paul D P and Pirastu, Nicola N and Pirie, Ailith and Pistis, Giorgio and Polasek, Ozren and Porteous, David and Psaty, Bruce M and Pylk{\"a}s, Katri and Radice, Paolo and Raffel, Leslie J and Rivadeneira, Fernando and Rudan, Igor and Rudolph, Anja and Ruggiero, Daniela and Sala, Cinzia F and Sanna, Serena and Sawyer, Elinor J and Schlessinger, David and Schmidt, Marjanka K and Schmidt, Frank and Schmutzler, Rita K and Schoemaker, Minouk J and Scott, Robert A and Seynaeve, Caroline M and Simard, Jacques and Sorice, Rossella and Southey, Melissa C and St{\"o}ckl, Doris and Strauch, Konstantin and Swerdlow, Anthony and Taylor, Kent D and Thorsteinsdottir, Unnur and Toland, Amanda E and Tomlinson, Ian and Truong, Therese and Tryggvadottir, Laufey and Turner, Stephen T and Vozzi, Diego and Wang, Qin and Wellons, Melissa and Willemsen, Gonneke and Wilson, James F and Winqvist, Robert and Wolffenbuttel, Bruce B H R and Wright, Alan F and Yannoukakos, Drakoulis and Zemunik, Tatijana and Zheng, Wei and Zygmunt, Marek and Bergmann, Sven and Boomsma, Dorret I and Buring, Julie E and Ferrucci, Luigi and Montgomery, Grant W and Gudnason, Vilmundur and Spector, Tim D and van Duijn, Cornelia M and Alizadeh, Behrooz Z and Ciullo, Marina and Crisponi, Laura and Easton, Douglas F and Gasparini, Paolo P and Gieger, Christian and Harris, Tamara B and Hayward, Caroline and Kardia, Sharon L R and Kraft, Peter and McKnight, Barbara and Metspalu, Andres and Morrison, Alanna C and Reiner, Alex P and Ridker, Paul M and Rotter, Jerome I and Toniolo, Daniela and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and V{\"o}lzke, Henry and Wareham, Nicholas J and Weir, David R and Yerges-Armstrong, Laura M and Price, Alkes L and Stefansson, Kari and Visser, Jenny A and Ong, Ken K and Chang-Claude, Jenny and Murabito, Joanne M and Perry, John R B and Murray, Anna} } @article {7736, title = {Rare coding variants and X-linked loci associated with age at menarche.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {7756}, abstract = {

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only \~{}3\% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6\%; effect sizes 0.08-1.25 years per allele; P<5 {\texttimes} 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 {\texttimes} 10(-13)) and FAAH2 (rs5914101, P=4.9 {\texttimes} 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 {\texttimes} 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain \~{}0.5\% variance, indicating that these overlooked sources of variation do not substantially explain the {\textquoteright}missing heritability{\textquoteright} of this complex trait.

}, issn = {2041-1723}, doi = {10.1038/ncomms8756}, author = {Lunetta, Kathryn L and Day, Felix R and Sulem, Patrick and Ruth, Katherine S and Tung, Joyce Y and Hinds, David A and Esko, T{\~o}nu and Elks, Cathy E and Altmaier, Elisabeth and He, Chunyan and Huffman, Jennifer E and Mihailov, Evelin and Porcu, Eleonora and Robino, Antonietta and Rose, Lynda M and Schick, Ursula M and Stolk, Lisette and Teumer, Alexander and Thompson, Deborah J and Traglia, Michela and Wang, Carol A and Yerges-Armstrong, Laura M and Antoniou, Antonis C and Barbieri, Caterina and Coviello, Andrea D and Cucca, Francesco and Demerath, Ellen W and Dunning, Alison M and Gandin, Ilaria and Grove, Megan L and Gudbjartsson, Daniel F and Hocking, Lynne J and Hofman, Albert and Huang, Jinyan and Jackson, Rebecca D and Karasik, David and Kriebel, Jennifer and Lange, Ethan M and Lange, Leslie A and Langenberg, Claudia and Li, Xin and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Morrison, Alanna C and Padmanabhan, Sandosh and Pirie, Ailith and Polasek, Ozren and Porteous, David and Reiner, Alex P and Rivadeneira, Fernando and Rudan, Igor and Sala, Cinzia F and Schlessinger, David and Scott, Robert A and St{\"o}ckl, Doris and Visser, Jenny A and V{\"o}lker, Uwe and Vozzi, Diego and Wilson, James G and Zygmunt, Marek and Boerwinkle, Eric and Buring, Julie E and Crisponi, Laura and Easton, Douglas F and Hayward, Caroline and Hu, Frank B and Liu, Simin and Metspalu, Andres and Pennell, Craig E and Ridker, Paul M and Strauch, Konstantin and Streeten, Elizabeth A and Toniolo, Daniela and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and V{\"o}lzke, Henry and Wareham, Nicholas J and Wellons, Melissa and Franceschini, Nora and Chasman, Daniel I and Thorsteinsdottir, Unnur and Murray, Anna and Stefansson, Kari and Murabito, Joanne M and Ong, Ken K and Perry, John R B} } @article {3593, title = {Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.}, journal = {Nature}, volume = {514}, year = {2014}, month = {2014 Oct 2}, pages = {92-7}, abstract = {

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 {\texttimes} 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.

}, keywords = {Adolescent, Age Factors, Alleles, Body Mass Index, Breast Neoplasms, Cardiovascular Diseases, Child, Diabetes Mellitus, Type 2, Europe, Female, Genetic Loci, Genome-Wide Association Study, Genomic Imprinting, Humans, Hypothalamo-Hypophyseal System, Intercellular Signaling Peptides and Proteins, Male, Membrane Proteins, Menarche, Obesity, Ovary, Parents, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain, Proteins, Quantitative Trait Loci, Receptors, GABA-B, Receptors, Retinoic Acid, Ribonucleoproteins}, issn = {1476-4687}, doi = {10.1038/nature13545}, author = {Perry, John R B and Day, Felix and Elks, Cathy E and Sulem, Patrick and Thompson, Deborah J and Ferreira, Teresa and He, Chunyan and Chasman, Daniel I and Esko, T{\~o}nu and Thorleifsson, Gudmar and Albrecht, Eva and Ang, Wei Q and Corre, Tanguy and Cousminer, Diana L and Feenstra, Bjarke and Franceschini, Nora and Ganna, Andrea and Johnson, Andrew D and Kjellqvist, Sanela and Lunetta, Kathryn L and McMahon, George and Nolte, Ilja M and Paternoster, Lavinia and Porcu, Eleonora and Smith, Albert V and Stolk, Lisette and Teumer, Alexander and T{\v s}ernikova, Natalia and Tikkanen, Emmi and Ulivi, Sheila and Wagner, Erin K and Amin, Najaf and Bierut, Laura J and Byrne, Enda M and Hottenga, Jouke-Jan and Koller, Daniel L and Mangino, Massimo and Pers, Tune H and Yerges-Armstrong, Laura M and Hua Zhao, Jing and Andrulis, Irene L and Anton-Culver, Hoda and Atsma, Femke and Bandinelli, Stefania and Beckmann, Matthias W and Benitez, Javier and Blomqvist, Carl and Bojesen, Stig E and Bolla, Manjeet K and Bonanni, Bernardo and Brauch, Hiltrud and Brenner, Hermann and Buring, Julie E and Chang-Claude, Jenny and Chanock, Stephen and Chen, Jinhui and Chenevix-Trench, Georgia and Coll{\'e}e, J Margriet and Couch, Fergus J and Couper, David and Coviello, Andrea D and Cox, Angela and Czene, Kamila and d{\textquoteright}Adamo, Adamo Pio and Davey Smith, George and De Vivo, Immaculata and Demerath, Ellen W and Dennis, Joe and Devilee, Peter and Dieffenbach, Aida K and Dunning, Alison M and Eiriksdottir, Gudny and Eriksson, Johan G and Fasching, Peter A and Ferrucci, Luigi and Flesch-Janys, Dieter and Flyger, Henrik and Foroud, Tatiana and Franke, Lude and Garcia, Melissa E and Garc{\'\i}a-Closas, Montserrat and Geller, Frank and de Geus, Eco E J and Giles, Graham G and Gudbjartsson, Daniel F and Gudnason, Vilmundur and Guenel, Pascal and Guo, Suiqun and Hall, Per and Hamann, Ute and Haring, Robin and Hartman, Catharina A and Heath, Andrew C and Hofman, Albert and Hooning, Maartje J and Hopper, John L and Hu, Frank B and Hunter, David J and Karasik, David and Kiel, Douglas P and Knight, Julia A and Kosma, Veli-Matti and Kutalik, Zolt{\'a}n and Lai, Sandra and Lambrechts, Diether and Lindblom, Annika and M{\"a}gi, Reedik and Magnusson, Patrik K and Mannermaa, Arto and Martin, Nicholas G and Masson, Gisli and McArdle, Patrick F and McArdle, Wendy L and Melbye, Mads and Michailidou, Kyriaki and Mihailov, Evelin and Milani, Lili and Milne, Roger L and Nevanlinna, Heli and Neven, Patrick and Nohr, Ellen A and Oldehinkel, Albertine J and Oostra, Ben A and Palotie, Aarno and Peacock, Munro and Pedersen, Nancy L and Peterlongo, Paolo and Peto, Julian and Pharoah, Paul D P and Postma, Dirkje S and Pouta, Anneli and Pylk{\"a}s, Katri and Radice, Paolo and Ring, Susan and Rivadeneira, Fernando and Robino, Antonietta and Rose, Lynda M and Rudolph, Anja and Salomaa, Veikko and Sanna, Serena and Schlessinger, David and Schmidt, Marjanka K and Southey, Mellissa C and Sovio, Ulla and Stampfer, Meir J and St{\"o}ckl, Doris and Storniolo, Anna M and Timpson, Nicholas J and Tyrer, Jonathan and Visser, Jenny A and Vollenweider, Peter and V{\"o}lzke, Henry and Waeber, Gerard and Waldenberger, Melanie and Wallaschofski, Henri and Wang, Qin and Willemsen, Gonneke and Winqvist, Robert and Wolffenbuttel, Bruce H R and Wright, Margaret J and Boomsma, Dorret I and Econs, Michael J and Khaw, Kay-Tee and Loos, Ruth J F and McCarthy, Mark I and Montgomery, Grant W and Rice, John P and Streeten, Elizabeth A and Thorsteinsdottir, Unnur and van Duijn, Cornelia M and Alizadeh, Behrooz Z and Bergmann, Sven and Boerwinkle, Eric and Boyd, Heather A and Crisponi, Laura and Gasparini, Paolo and Gieger, Christian and Harris, Tamara B and Ingelsson, Erik and J{\"a}rvelin, Marjo-Riitta and Kraft, Peter and Lawlor, Debbie and Metspalu, Andres and Pennell, Craig E and Ridker, Paul M and Snieder, Harold and S{\o}rensen, Thorkild I A and Spector, Tim D and Strachan, David P and Uitterlinden, Andr{\'e} G and Wareham, Nicholas J and Widen, Elisabeth and Zygmunt, Marek and Murray, Anna and Easton, Douglas F and Stefansson, Kari and Murabito, Joanne M and Ong, Ken K} } @article {1906, title = {Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.}, journal = {Nat Genet}, volume = {44}, year = {2012}, month = {2012 Mar}, pages = {260-8}, abstract = {

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 {\texttimes} 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

}, keywords = {Age Factors, DNA Helicases, DNA Primase, DNA Repair, DNA Repair Enzymes, DNA-Directed DNA Polymerase, European Continental Ancestry Group, Exodeoxyribonucleases, Female, Genetic Loci, Genome-Wide Association Study, Humans, Immunity, Menopause, Polymorphism, Single Nucleotide, Proteins}, issn = {1546-1718}, doi = {10.1038/ng.1051}, author = {Stolk, Lisette and Perry, John R B and Chasman, Daniel I and He, Chunyan and Mangino, Massimo and Sulem, Patrick and Barbalic, Maja and Broer, Linda and Byrne, Enda M and Ernst, Florian and Esko, T{\~o}nu and Franceschini, Nora and Gudbjartsson, Daniel F and Hottenga, Jouke-Jan and Kraft, Peter and McArdle, Patrick F and Porcu, Eleonora and Shin, So-Youn and Smith, Albert V and van Wingerden, Sophie and Zhai, Guangju and Zhuang, Wei V and Albrecht, Eva and Alizadeh, Behrooz Z and Aspelund, Thor and Bandinelli, Stefania and Lauc, Lovorka Barac and Beckmann, Jacques S and Boban, Mladen and Boerwinkle, Eric and Broekmans, Frank J and Burri, Andrea and Campbell, Harry and Chanock, Stephen J and Chen, Constance and Cornelis, Marilyn C and Corre, Tanguy and Coviello, Andrea D and d{\textquoteright}Adamo, Pio and Davies, Gail and de Faire, Ulf and de Geus, Eco J C and Deary, Ian J and Dedoussis, George V Z and Deloukas, Panagiotis and Ebrahim, Shah and Eiriksdottir, Gudny and Emilsson, Valur and Eriksson, Johan G and Fauser, Bart C J M and Ferreli, Liana and Ferrucci, Luigi and Fischer, Krista and Folsom, Aaron R and Garcia, Melissa E and Gasparini, Paolo and Gieger, Christian and Glazer, Nicole and Grobbee, Diederick E and Hall, Per and Haller, Toomas and Hankinson, Susan E and Hass, Merli and Hayward, Caroline and Heath, Andrew C and Hofman, Albert and Ingelsson, Erik and Janssens, A Cecile J W and Johnson, Andrew D and Karasik, David and Kardia, Sharon L R and Keyzer, Jules and Kiel, Douglas P and Kolcic, Ivana and Kutalik, Zolt{\'a}n and Lahti, Jari and Lai, Sandra and Laisk, Triin and Laven, Joop S E and Lawlor, Debbie A and Liu, Jianjun and Lopez, Lorna M and Louwers, Yvonne V and Magnusson, Patrik K E and Marongiu, Mara and Martin, Nicholas G and Klaric, Irena Martinovic and Masciullo, Corrado and McKnight, Barbara and Medland, Sarah E and Melzer, David and Mooser, Vincent and Navarro, Pau and Newman, Anne B and Nyholt, Dale R and Onland-Moret, N Charlotte and Palotie, Aarno and Par{\'e}, Guillaume and Parker, Alex N and Pedersen, Nancy L and Peeters, Petra H M and Pistis, Giorgio and Plump, Andrew S and Polasek, Ozren and Pop, Victor J M and Psaty, Bruce M and R{\"a}ikk{\"o}nen, Katri and Rehnberg, Emil and Rotter, Jerome I and Rudan, Igor and Sala, Cinzia and Salumets, Andres and Scuteri, Angelo and Singleton, Andrew and Smith, Jennifer A and Snieder, Harold and Soranzo, Nicole and Stacey, Simon N and Starr, John M and Stathopoulou, Maria G and Stirrups, Kathleen and Stolk, Ronald P and Styrkarsdottir, Unnur and Sun, Yan V and Tenesa, Albert and Thorand, Barbara and Toniolo, Daniela and Tryggvadottir, Laufey and Tsui, Kim and Ulivi, Sheila and van Dam, Rob M and van der Schouw, Yvonne T and van Gils, Carla H and van Nierop, Peter and Vink, Jacqueline M and Visscher, Peter M and Voorhuis, Marlies and Waeber, Gerard and Wallaschofski, Henri and Wichmann, H Erich and Widen, Elisabeth and Wijnands-van Gent, Colette J M and Willemsen, Gonneke and Wilson, James F and Wolffenbuttel, Bruce H R and Wright, Alan F and Yerges-Armstrong, Laura M and Zemunik, Tatijana and Zgaga, Lina and Zillikens, M Carola and Zygmunt, Marek and Arnold, Alice M and Boomsma, Dorret I and Buring, Julie E and Crisponi, Laura and Demerath, Ellen W and Gudnason, Vilmundur and Harris, Tamara B and Hu, Frank B and Hunter, David J and Launer, Lenore J and Metspalu, Andres and Montgomery, Grant W and Oostra, Ben A and Ridker, Paul M and Sanna, Serena and Schlessinger, David and Spector, Tim D and Stefansson, Kari and Streeten, Elizabeth A and Thorsteinsdottir, Unnur and Uda, Manuela and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and V{\"o}lzke, Henry and Murray, Anna and Murabito, Joanne M and Visser, Jenny A and Lunetta, Kathryn L} } @article {1734, title = {Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.}, journal = {Nat Genet}, volume = {42}, year = {2010}, month = {2010 Dec}, pages = {1077-85}, abstract = {

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 {\texttimes} 10$^{-}$$^{6}$$^{0}$) and 9q31.2 (P = 2.2 {\texttimes} 10$^{-}${\textthreesuperior}{\textthreesuperior}), we identified 30 new menarche loci (all P < 5 {\texttimes} 10$^{-}$$^{8}$) and found suggestive evidence for a further 10 loci (P < 1.9 {\texttimes} 10$^{-}$$^{6}$). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

}, keywords = {Adolescent, Aging, Body Height, Body Size, Child, DNA Copy Number Variations, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inheritance Patterns, Menarche, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Time Factors}, issn = {1546-1718}, doi = {10.1038/ng.714}, author = {Elks, Cathy E and Perry, John R B and Sulem, Patrick and Chasman, Daniel I and Franceschini, Nora and He, Chunyan and Lunetta, Kathryn L and Visser, Jenny A and Byrne, Enda M and Cousminer, Diana L and Gudbjartsson, Daniel F and Esko, T{\~o}nu and Feenstra, Bjarke and Hottenga, Jouke-Jan and Koller, Daniel L and Kutalik, Zolt{\'a}n and Lin, Peng and Mangino, Massimo and Marongiu, Mara and McArdle, Patrick F and Smith, Albert V and Stolk, Lisette and van Wingerden, Sophie H and Zhao, Jing Hua and Albrecht, Eva and Corre, Tanguy and Ingelsson, Erik and Hayward, Caroline and Magnusson, Patrik K E and Smith, Erin N and Ulivi, Shelia and Warrington, Nicole M and Zgaga, Lina and Alavere, Helen and Amin, Najaf and Aspelund, Thor and Bandinelli, Stefania and Barroso, In{\^e}s and Berenson, Gerald S and Bergmann, Sven and Blackburn, Hannah and Boerwinkle, Eric and Buring, Julie E and Busonero, Fabio and Campbell, Harry and Chanock, Stephen J and Chen, Wei and Cornelis, Marilyn C and Couper, David and Coviello, Andrea D and d{\textquoteright}Adamo, Pio and de Faire, Ulf and de Geus, Eco J C and Deloukas, Panos and D{\"o}ring, Angela and Smith, George Davey and Easton, Douglas F and Eiriksdottir, Gudny and Emilsson, Valur and Eriksson, Johan and Ferrucci, Luigi and Folsom, Aaron R and Foroud, Tatiana and Garcia, Melissa and Gasparini, Paolo and Geller, Frank and Gieger, Christian and Gudnason, Vilmundur and Hall, Per and Hankinson, Susan E and Ferreli, Liana and Heath, Andrew C and Hernandez, Dena G and Hofman, Albert and Hu, Frank B and Illig, Thomas and J{\"a}rvelin, Marjo-Riitta and Johnson, Andrew D and Karasik, David and Khaw, Kay-Tee and Kiel, Douglas P and Kilpel{\"a}inen, Tuomas O and Kolcic, Ivana and Kraft, Peter and Launer, Lenore J and Laven, Joop S E and Li, Shengxu and Liu, Jianjun and Levy, Daniel and Martin, Nicholas G and McArdle, Wendy L and Melbye, Mads and Mooser, Vincent and Murray, Jeffrey C and Murray, Sarah S and Nalls, Michael A and Navarro, Pau and Nelis, Mari and Ness, Andrew R and Northstone, Kate and Oostra, Ben A and Peacock, Munro and Palmer, Lyle J and Palotie, Aarno and Par{\'e}, Guillaume and Parker, Alex N and Pedersen, Nancy L and Peltonen, Leena and Pennell, Craig E and Pharoah, Paul and Polasek, Ozren and Plump, Andrew S and Pouta, Anneli and Porcu, Eleonora and Rafnar, Thorunn and Rice, John P and Ring, Susan M and Rivadeneira, Fernando and Rudan, Igor and Sala, Cinzia and Salomaa, Veikko and Sanna, Serena and Schlessinger, David and Schork, Nicholas J and Scuteri, Angelo and Segr{\`e}, Ayellet V and Shuldiner, Alan R and Soranzo, Nicole and Sovio, Ulla and Srinivasan, Sathanur R and Strachan, David P and Tammesoo, Mar-Liis and Tikkanen, Emmi and Toniolo, Daniela and Tsui, Kim and Tryggvadottir, Laufey and Tyrer, Jonathon and Uda, Manuela and van Dam, Rob M and van Meurs, Joyce B J and Vollenweider, Peter and Waeber, Gerard and Wareham, Nicholas J and Waterworth, Dawn M and Weedon, Michael N and Wichmann, H Erich and Willemsen, Gonneke and Wilson, James F and Wright, Alan F and Young, Lauren and Zhai, Guangju and Zhuang, Wei Vivian and Bierut, Laura J and Boomsma, Dorret I and Boyd, Heather A and Crisponi, Laura and Demerath, Ellen W and van Duijn, Cornelia M and Econs, Michael J and Harris, Tamara B and Hunter, David J and Loos, Ruth J F and Metspalu, Andres and Montgomery, Grant W and Ridker, Paul M and Spector, Tim D and Streeten, Elizabeth A and Stefansson, Kari and Thorsteinsdottir, Unnur and Uitterlinden, Andr{\'e} G and Widen, Elisabeth and Murabito, Joanne M and Ong, Ken K and Murray, Anna} }