TY - JOUR
T1 - Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan
AU - Australian Prostate Cancer BioResource (APCB)
AU - The PRACTICAL Consortium
AU - 23andMe Research Team
AU - Hollis, Ben
AU - Day, Felix R.
AU - Busch, Alexander S.
AU - Thompson, Deborah J.
AU - Soares, Ana Luiza G.
AU - Timmers, Paul R.H.J.
AU - Kwong, Alex
AU - Easton, Doug F.
AU - Joshi, Peter K.
AU - Timpson, Nicholas J.
AU - Eeles, Rosalind A.
AU - Henderson, Brian E.
AU - Haiman, Christopher A.
AU - Kote-Jarai, Zsofia
AU - Schumacher, Fredrick R.
AU - Olama, Ali Amin Al
AU - Benlloch, Sara
AU - Muir, Kenneth
AU - Berndt, Sonja I.
AU - Conti, David V.
AU - Wiklund, Fredrik
AU - Chanock, Stephen
AU - Gapstur, Susan
AU - Stevens, Victoria L.
AU - Tangen, Catherine M.
AU - Batra, Jyotsna
AU - Clements, Judith
AU - Gronberg, Henrik
AU - Pashayan, Nora
AU - Schleutker, Johanna
AU - Albanes, Demetrius
AU - Wolk, Alicja
AU - West, Catharine
AU - Mucci, Lorelei
AU - Cancel-Tassin, Géraldine
AU - Koutros, Stella
AU - Sorensen, Karina Dalsgaard
AU - Grindedal, Eli Marie
AU - Neal, David E.
AU - Hamdy, Freddie C.
AU - Donovan, Jenny L.
AU - Travis, Ruth C.
AU - Hamilton, Robert J.
AU - Ingles, Sue Ann
AU - Rosenstein, Barry S.
AU - Lu, Yong Jie
AU - Giles, Graham G.
AU - Kibel, Adam S.
AU - Vega, Ana
AU - Thibodeau, Stephen N.
N1 - Funding Information:
This work was funded by the UK Medical Research Council (MRC; Unit programme MC_UU_12015/2) and used UK Biobank data under application 9905. The MRC, Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and <John Perry and Ken Ong> will serve as guarantors for the contents of this paper. GWAS data for ALSPAC was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. We are extremely grateful to all the families who took part in the ALSPAC study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research assistants, volunteers, managers, receptionists and nurses. We thank the research participants and employees of 23andMe for making this work possible. Geno-typing of the OncoArray was funded by the US National Institutes of Health (NIH) [U19 CA154 148537 for ELucidating Loci Involved in Prostate cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number 156 HHSN268201200008I]. Additional analytic support was provided by NIH NCI U01 CA188392 157 (PI: Schumacher). The PRACTICAL consortium was supported by Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, European 160 Commission’s Seventh Framework Programme grant agreement no° 223175 (HEALTH-F2-2009-223175), and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. In memoriam: Brian E. Henderson.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-14451-5
DO - 10.1038/s41467-020-14451-5
M3 - Article
C2 - 32210231
AN - SCOPUS:85082380708
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1536
ER -