Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

• Published in: Nature communications Vol. 11; no. 1; p. 1536
• Main 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., Ong, Ken K., Perry, John R. B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.03.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/205/2138; 631/443/494; 692/163; 692/308/2056; Adult; Age; Age Factors; Cohort Studies; Color; Female; Genetic analysis; Genetic control; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomic analysis; Hair; Hair Color - genetics; Hormones; Humanities and Social Sciences; Humans; Life span; Longevity - genetics; Male; Men; Menarche; Menarche - genetics; Mendelian Randomization Analysis; multidisciplinary; Phenotypes; Pigmentation; Pituitary; Pituitary hormones; Polymorphism, Single Nucleotide; Puberty; Puberty - genetics; Science; Science (multidisciplinary); Sexual Maturation - genetics; Time Factors; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14451-5

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. Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.