PT  - JOURNAL ARTICLE
AU  - Ben Hollis
AU  - Felix R. Day
AU  - Alexander S. Busch
AU  - Deborah J. Thompson
AU  - Ana Luiza G. Soares
AU  - Paul R.H.J. Timmers
AU  - Alex Kwong
AU  - Doug F. Easton
AU  - Peter K. Joshi
AU  - Nicholas J. Timpson
AU  - The PRACTICAL Consortium
AU  - 23andMe Research Team
AU  - Ken K. Ong
AU  - John R.B. Perry
TI  - Expanded genomic analyses for male voice-breaking highlights a shared phenotypic and genetic basis between puberty timing and hair colour
AID  - 10.1101/483933
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 483933
4099  - http://biorxiv.org/content/early/2018/12/13/483933.short
4100  - http://biorxiv.org/content/early/2018/12/13/483933.full
AB  - The timing of puberty is highly variable and has important consequences for long-term health. Most of our understanding of the genetic control of puberty timing is based on studies in women, as age at menarche is often recorded. Here, we report a multi-trait genome-wide association study for male puberty timing, based on recalled timing of voice breaking and facial hair, with an effective sample size of 205,354 men, nearly four-fold larger than previously reported. We identify 78 independent signals for male puberty timing, including 29 signals not previously associated with puberty in either sex. Novel mechanisms include an unexpected phenotypic and genetic 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, in Mendelian randomization analyses, shows causal relationships with higher risk of prostate cancer and shorter lifespan. These findings highlight the relationships between puberty timing and later health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.