Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan
Ben Hollis, Felix R. Day, Alexander S. Busch, Deborah J. Thompson, Ana Gonçalves Soares, Paul R. H. J. Timmers, Alex S. F. Kwong, Doug Easton, Peter K. Joshi, Nicholas J. Timpson, Rosalind A. Eeles, Brian E. Henderson, Christopher A. Haiman, Zsofia Kote‐Jarai, Fredrick R. Schumacher, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen Chanock, Susan M. Gapstur, Victoria L. Stevens, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, Australian Prostate Cancer BioResource (APCB), Wayne D. Tilley, Gail P. Risbridger, Judith A. Clements, Lisa G. Horvath, Renea A. Taylor, Vanessa M. Hayes, Lisa M. Butler, Trina Yeadon, Allison Eckert, Pâmela Saunders, Anne‐Maree Haynes, Melissa Papargiris, Srilakshmi Srinivasan, Mary‐Anne Kedda, Leire Moya, Jyotsna Batra, Henrik Grönberg, Nora Pashayan, Johanna Schleutker, Demetrius Albanes, Alicja Wolk, Catharine West, Lorelei A. Mucci, Géraldine Cancel‐Tassin, Stella Koutros, Karina D. Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Hermann Brenner, Christiane Maier, Jeri Kim, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Hassan Abdul Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago-Domínguez, Monique J. Roobol, F. Ménégaux, Kay-Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas
Abstract
The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.