Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan
Authors: Hollis Ben , Day Felix R. , Busch Alexander S. , Thompson Deborah J. , Soares Ana Luiza G. , Timmers Paul R. H. J. , Kwong Alex , Easton Doug F. , Joshi Peter K. , Timpson Nicholas J. ,   The PRACTICAL Consortium, Eeles Rosalind A. , Henderson Brian E. , Haiman Christopher A. , Kote-Jarai Zsofia , Schumacher Fredrick R. , Olama Ali Amin Al , Benlloch Sara , Muir Kenneth , Berndt Sonja I. , Conti David V. , Wiklund Fredrik , Chanock Stephen , Gapstur Susan , Stevens Victoria L. , Tangen Catherine M. , Batra Jyotsna , Clements Judith ,   Australian Prostate Cancer BioResource (APCB), Tilley Wayne , Risbridger Gail P. , Clements Judith , Horvath Lisa , Taylor Renea , Hayes Vanessa , Butler Lisa , Yeadon Trina , Eckert Allison , Saunders Pamela , Haynes Anne-Maree , Papargiris Melissa , Srinivasan Srilakshmi , Kedda Mary-Anne , Moya Leire , Batra Jyotsna , Gronberg Henrik , Pashayan Nora , Schleutker Johanna , Albanes Demetrius , Wolk Alicja , West Catharine , Mucci Lorelei , Cancel-Tassin Géraldine , Koutros Stella , Sorensen Karina Dalsgaard , Grindedal Eli Marie , Neal David E. , Hamdy Freddie C. , Donovan Jenny L. , Travis Ruth C. , Hamilton Robert J. , Ingles Sue Ann , Rosenstein Barry S. , Lu Yong-Jie , Giles Graham G. , Kibel Adam S. , Vega Ana , Kogevinas Manolis , Penney Kathryn L. , Park Jong Y. , Stanford Janet L. , Cybulski Cezary , Nordestgaard Børge G. , Brenner Hermann , Maier Christiane , Kim Jeri , John Esther M. , Teixeira Manuel R. , Neuhausen Susan L. , De Ruyck Kim , Razack Azad , Newcomb Lisa F. , Lessel Davor , Kaneva Radka , Usmani Nawaid , Claessens Frank , Townsend Paul A. , Gago-Dominguez Manuela , Roobol Monique J. , Menegaux Florence , Khaw Kay-Tee , Cannon-Albright Lisa , Pandha Hardev , Thibodeau Stephen N. ,   23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Hinds David A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Vacic Vladimir , Wilson Catherine H. , Ong Ken K. , Perry John R. B. 
Published: March 2020

AbstractThe 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.