%0 Journal Article %J PLoS One %D 2018 %T Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. %A Feitosa, Mary F %A Kraja, Aldi T %A Chasman, Daniel I %A Sung, Yun J %A Winkler, Thomas W %A Ntalla, Ioanna %A Guo, Xiuqing %A Franceschini, Nora %A Cheng, Ching-Yu %A Sim, Xueling %A Vojinovic, Dina %A Marten, Jonathan %A Musani, Solomon K %A Li, Changwei %A Bentley, Amy R %A Brown, Michael R %A Schwander, Karen %A Richard, Melissa A %A Noordam, Raymond %A Aschard, Hugues %A Bartz, Traci M %A Bielak, Lawrence F %A Dorajoo, Rajkumar %A Fisher, Virginia %A Hartwig, Fernando P %A Horimoto, Andrea R V R %A Lohman, Kurt K %A Manning, Alisa K %A Rankinen, Tuomo %A Smith, Albert V %A Tajuddin, Salman M %A Wojczynski, Mary K %A Alver, Maris %A Boissel, Mathilde %A Cai, Qiuyin %A Campbell, Archie %A Chai, Jin Fang %A Chen, Xu %A Divers, Jasmin %A Gao, Chuan %A Goel, Anuj %A Hagemeijer, Yanick %A Harris, Sarah E %A He, Meian %A Hsu, Fang-Chi %A Jackson, Anne U %A Kähönen, Mika %A Kasturiratne, Anuradhani %A Komulainen, Pirjo %A Kuhnel, Brigitte %A Laguzzi, Federica %A Luan, Jian'an %A Matoba, Nana %A Nolte, Ilja M %A Padmanabhan, Sandosh %A Riaz, Muhammad %A Rueedi, Rico %A Robino, Antonietta %A Said, M Abdullah %A Scott, Robert A %A Sofer, Tamar %A Stančáková, Alena %A Takeuchi, Fumihiko %A Tayo, Bamidele O %A van der Most, Peter J %A Varga, Tibor V %A Vitart, Veronique %A Wang, Yajuan %A Ware, Erin B %A Warren, Helen R %A Weiss, Stefan %A Wen, Wanqing %A Yanek, Lisa R %A Zhang, Weihua %A Zhao, Jing Hua %A Afaq, Saima %A Amin, Najaf %A Amini, Marzyeh %A Arking, Dan E %A Aung, Tin %A Boerwinkle, Eric %A Borecki, Ingrid %A Broeckel, Ulrich %A Brown, Morris %A Brumat, Marco %A Burke, Gregory L %A Canouil, Mickaël %A Chakravarti, Aravinda %A Charumathi, Sabanayagam %A Ida Chen, Yii-Der %A Connell, John M %A Correa, Adolfo %A de Las Fuentes, Lisa %A de Mutsert, Renée %A de Silva, H Janaka %A Deng, Xuan %A Ding, Jingzhong %A Duan, Qing %A Eaton, Charles B %A Ehret, Georg %A Eppinga, Ruben N %A Evangelou, Evangelos %A Faul, Jessica D %A Felix, Stephan B %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Friedlander, Yechiel %A Gandin, Ilaria %A Gao, He %A Ghanbari, Mohsen %A Gigante, Bruna %A Gu, C Charles %A Gu, Dongfeng %A Hagenaars, Saskia P %A Hallmans, Goran %A Harris, Tamara B %A He, Jiang %A Heikkinen, Sami %A Heng, Chew-Kiat %A Hirata, Makoto %A Howard, Barbara V %A Ikram, M Arfan %A John, Ulrich %A Katsuya, Tomohiro %A Khor, Chiea Chuen %A Kilpeläinen, Tuomas O %A Koh, Woon-Puay %A Krieger, Jose E %A Kritchevsky, Stephen B %A Kubo, Michiaki %A Kuusisto, Johanna %A Lakka, Timo A %A Langefeld, Carl D %A Langenberg, Claudia %A Launer, Lenore J %A Lehne, Benjamin %A Lewis, Cora E %A Li, Yize %A Lin, Shiow %A Liu, Jianjun %A Liu, Jingmin %A Loh, Marie %A Louie, Tin %A Mägi, Reedik %A McKenzie, Colin A %A Meitinger, Thomas %A Metspalu, Andres %A Milaneschi, Yuri %A Milani, Lili %A Mohlke, Karen L %A Momozawa, Yukihide %A Nalls, Mike A %A Nelson, Christopher P %A Sotoodehnia, Nona %A Norris, Jill M %A O'Connell, Jeff R %A Palmer, Nicholette D %A Perls, Thomas %A Pedersen, Nancy L %A Peters, Annette %A Peyser, Patricia A %A Poulter, Neil %A Raffel, Leslie J %A Raitakari, Olli T %A Roll, Kathryn %A Rose, Lynda M %A Rosendaal, Frits R %A Rotter, Jerome I %A Schmidt, Carsten O %A Schreiner, Pamela J %A Schupf, Nicole %A Scott, William R %A Sever, Peter S %A Shi, Yuan %A Sidney, Stephen %A Sims, Mario %A Sitlani, Colleen M %A Smith, Jennifer A %A Snieder, Harold %A Starr, John M %A Strauch, Konstantin %A Stringham, Heather M %A Tan, Nicholas Y Q %A Tang, Hua %A Taylor, Kent D %A Teo, Yik Ying %A Tham, Yih Chung %A Turner, Stephen T %A Uitterlinden, André G %A Vollenweider, Peter %A Waldenberger, Melanie %A Wang, Lihua %A Wang, Ya Xing %A Wei, Wen Bin %A Williams, Christine %A Yao, Jie %A Yu, Caizheng %A Yuan, Jian-Min %A Zhao, Wei %A Zonderman, Alan B %A Becker, Diane M %A Boehnke, Michael %A Bowden, Donald W %A Chambers, John C %A Deary, Ian J %A Esko, Tõnu %A Farrall, Martin %A Franks, Paul W %A Freedman, Barry I %A Froguel, Philippe %A Gasparini, Paolo %A Gieger, Christian %A Jonas, Jost Bruno %A Kamatani, Yoichiro %A Kato, Norihiro %A Kooner, Jaspal S %A Kutalik, Zoltán %A Laakso, Markku %A Laurie, Cathy C %A Leander, Karin %A Lehtimäki, Terho %A Study, Lifelines Cohort %A Magnusson, Patrik K E %A Oldehinkel, Albertine J %A Penninx, Brenda W J H %A Polasek, Ozren %A Porteous, David J %A Rauramaa, Rainer %A Samani, Nilesh J %A Scott, James %A Shu, Xiao-Ou %A van der Harst, Pim %A Wagenknecht, Lynne E %A Wareham, Nicholas J %A Watkins, Hugh %A Weir, David R %A Wickremasinghe, Ananda R %A Wu, Tangchun %A Zheng, Wei %A Bouchard, Claude %A Christensen, Kaare %A Evans, Michele K %A Gudnason, Vilmundur %A Horta, Bernardo L %A Kardia, Sharon L R %A Liu, Yongmei %A Pereira, Alexandre C %A Psaty, Bruce M %A Ridker, Paul M %A van Dam, Rob M %A Gauderman, W James %A Zhu, Xiaofeng %A Mook-Kanamori, Dennis O %A Fornage, Myriam %A Rotimi, Charles N %A Cupples, L Adrienne %A Kelly, Tanika N %A Fox, Ervin R %A Hayward, Caroline %A van Duijn, Cornelia M %A Tai, E Shyong %A Wong, Tien Yin %A Kooperberg, Charles %A Palmas, Walter %A Rice, Kenneth %A Morrison, Alanna C %A Elliott, Paul %A Caulfield, Mark J %A Munroe, Patricia B %A Rao, Dabeeru C %A Province, Michael A %A Levy, Daniel %K Adolescent %K Adult %K Aged %K Aged, 80 and over %K Alcohol Drinking %K Blood Pressure %K Cohort Studies %K Continental Population Groups %K Female %K Gene-Environment Interaction %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Humans %K Hypertension %K Male %K Middle Aged %K Pedigree %K Polymorphism, Single Nucleotide %K Young Adult %X

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.

%B PLoS One %V 13 %P e0198166 %8 2018 %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/29912962?dopt=Abstract %R 10.1371/journal.pone.0198166 %0 Journal Article %J Nat Genet %D 2017 %T Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. %A Day, Felix R %A Thompson, Deborah J %A Helgason, Hannes %A Chasman, Daniel I %A Finucane, Hilary %A Sulem, Patrick %A Ruth, Katherine S %A Whalen, Sean %A Sarkar, Abhishek K %A Albrecht, Eva %A Altmaier, Elisabeth %A Amini, Marzyeh %A Barbieri, Caterina M %A Boutin, Thibaud %A Campbell, Archie %A Demerath, Ellen %A Giri, Ayush %A He, Chunyan %A Hottenga, Jouke J %A Karlsson, Robert %A Kolcic, Ivana %A Loh, Po-Ru %A Lunetta, Kathryn L %A Mangino, Massimo %A Marco, Brumat %A McMahon, George %A Medland, Sarah E %A Nolte, Ilja M %A Noordam, Raymond %A Nutile, Teresa %A Paternoster, Lavinia %A Perjakova, Natalia %A Porcu, Eleonora %A Rose, Lynda M %A Schraut, Katharina E %A Segrè, Ayellet V %A Smith, Albert V %A Stolk, Lisette %A Teumer, Alexander %A Andrulis, Irene L %A Bandinelli, Stefania %A Beckmann, Matthias W %A Benitez, Javier %A Bergmann, Sven %A Bochud, Murielle %A Boerwinkle, Eric %A Bojesen, Stig E %A Bolla, Manjeet K %A Brand, Judith S %A Brauch, Hiltrud %A Brenner, Hermann %A Broer, Linda %A Brüning, Thomas %A Buring, Julie E %A Campbell, Harry %A Catamo, Eulalia %A Chanock, Stephen %A Chenevix-Trench, Georgia %A Corre, Tanguy %A Couch, Fergus J %A Cousminer, Diana L %A Cox, Angela %A Crisponi, Laura %A Czene, Kamila %A Davey Smith, George %A de Geus, Eco J C N %A de Mutsert, Renée %A De Vivo, Immaculata %A Dennis, Joe %A Devilee, Peter %A Dos-Santos-Silva, Isabel %A Dunning, Alison M %A Eriksson, Johan G %A Fasching, Peter A %A Fernández-Rhodes, Lindsay %A Ferrucci, Luigi %A Flesch-Janys, Dieter %A Franke, Lude %A Gabrielson, Marike %A Gandin, Ilaria %A Giles, Graham G %A Grallert, Harald %A Gudbjartsson, Daniel F %A Guenel, Pascal %A Hall, Per %A Hallberg, Emily %A Hamann, Ute %A Harris, Tamara B %A Hartman, Catharina A %A Heiss, Gerardo %A Hooning, Maartje J %A Hopper, John L %A Hu, Frank %A Hunter, David J %A Ikram, M Arfan %A Im, Hae Kyung %A Järvelin, Marjo-Riitta %A Joshi, Peter K %A Karasik, David %A Kellis, Manolis %A Kutalik, Zoltán %A LaChance, Genevieve %A Lambrechts, Diether %A Langenberg, Claudia %A Launer, Lenore J %A Laven, Joop S E %A Lenarduzzi, Stefania %A Li, Jingmei %A Lind, Penelope A %A Lindström, Sara %A Liu, Yongmei %A Luan, Jian'an %A Mägi, Reedik %A Mannermaa, Arto %A Mbarek, Hamdi %A McCarthy, Mark I %A Meisinger, Christa %A Meitinger, Thomas %A Menni, Cristina %A Metspalu, Andres %A Michailidou, Kyriaki %A Milani, Lili %A Milne, Roger L %A Montgomery, Grant W %A Mulligan, Anna M %A Nalls, Mike A %A Navarro, Pau %A Nevanlinna, Heli %A Nyholt, Dale R %A Oldehinkel, Albertine J %A O'Mara, Tracy A %A Padmanabhan, Sandosh %A Palotie, Aarno %A Pedersen, Nancy %A Peters, Annette %A Peto, Julian %A Pharoah, Paul D P %A Pouta, Anneli %A Radice, Paolo %A Rahman, Iffat %A Ring, Susan M %A Robino, Antonietta %A Rosendaal, Frits R %A Rudan, Igor %A Rueedi, Rico %A Ruggiero, Daniela %A Sala, Cinzia F %A Schmidt, Marjanka K %A Scott, Robert A %A Shah, Mitul %A Sorice, Rossella %A Southey, Melissa C %A Sovio, Ulla %A Stampfer, Meir %A Steri, Maristella %A Strauch, Konstantin %A Tanaka, Toshiko %A Tikkanen, Emmi %A Timpson, Nicholas J %A Traglia, Michela %A Truong, Therese %A Tyrer, Jonathan P %A Uitterlinden, André G %A Edwards, Digna R Velez %A Vitart, Veronique %A Völker, Uwe %A Vollenweider, Peter %A Wang, Qin %A Widen, Elisabeth %A van Dijk, Ko Willems %A Willemsen, Gonneke %A Winqvist, Robert %A Wolffenbuttel, Bruce H R %A Zhao, Jing Hua %A Zoledziewska, Magdalena %A Zygmunt, Marek %A Alizadeh, Behrooz Z %A Boomsma, Dorret I %A Ciullo, Marina %A Cucca, Francesco %A Esko, Tõnu %A Franceschini, Nora %A Gieger, Christian %A Gudnason, Vilmundur %A Hayward, Caroline %A Kraft, Peter %A Lawlor, Debbie A %A Magnusson, Patrik K E %A Martin, Nicholas G %A Mook-Kanamori, Dennis O %A Nohr, Ellen A %A Polasek, Ozren %A Porteous, David %A Price, Alkes L %A Ridker, Paul M %A Snieder, Harold %A Spector, Tim D %A Stöckl, Doris %A Toniolo, Daniela %A Ulivi, Sheila %A Visser, Jenny A %A Völzke, Henry %A Wareham, Nicholas J %A Wilson, James F %A Spurdle, Amanda B %A Thorsteindottir, Unnur %A Pollard, Katherine S %A Easton, Douglas F %A Tung, Joyce Y %A Chang-Claude, Jenny %A Hinds, David %A Murray, Anna %A Murabito, Joanne M %A Stefansson, Kari %A Ong, Ken K %A Perry, John R B %K Adolescent %K Age Factors %K Body Mass Index %K Databases, Genetic %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Genomic Imprinting %K Humans %K Intercellular Signaling Peptides and Proteins %K Male %K Membrane Proteins %K Menarche %K Neoplasms %K Polymorphism, Single Nucleotide %K Puberty %K Quantitative Trait Loci %K Ribonucleoproteins %K Risk Factors %X

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 × 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.

%B Nat Genet %V 49 %P 834-841 %8 2017 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/28436984?dopt=Abstract %R 10.1038/ng.3841 %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