Shared genetic aetiology of puberty timing between sexes and with health-related outcomes.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Day, Felix R; Bulik-Sullivan, Brendan; Hinds, David A; Finucane, Hilary K; Murabito, Joanne M; Tung, Joyce Y; Ong, Ken K; Perry, John R B
Year of Publication: 2015
Journal: Nat Commun
Volume: 6
Pagination: 8842
Date Published: 2015
Publication Language: eng
ISSN: 2041-1723
Keywords: Adolescent, Basic Helix-Loop-Helix Transcription Factors, Body Height, Body Mass Index, Bone Density, Cardiovascular Diseases, Child, Cholesterol, HDL, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Extracellular Matrix Proteins, Female, Genome-Wide Association Study, Humans, Insulin, Lumbar Vertebrae, Male, Nerve Tissue Proteins, Nuclear Receptor Subfamily 1, Group F, Member 2, Polycystic Ovary Syndrome, Puberty, Receptors, G-Protein-Coupled, Receptors, Leptin, Receptors, Pituitary Hormone, Repressor Proteins, Retinoid X Receptor alpha, Sex Factors, Time Factors, Triglycerides, Young Adult

Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10(-12)). We find five novel loci for puberty timing (P<5 × 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease.

DOI: 10.1038/ncomms9842
Alternate Journal: Nat Commun