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


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Authors

Day, Felix R 
Bulik-Sullivan, Brendan 
Hinds, David A 
Finucane, Hilary K 
Murabito, Joanne M 

Abstract

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.

Description

Keywords

Adolescent, Basic Helix-Loop-Helix Transcription Factors, Body Height, Body Mass Index, Bone Density, Cardiovascular Diseases, Child, Cholesterol, HDL, Diabetes Mellitus, Type 2, 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, Radiography, Receptors, G-Protein-Coupled, Receptors, Leptin, Receptors, Pituitary Hormone, Repressor Proteins, Retinoid X Receptor alpha, Sex Factors, Time Factors, Triglycerides, White People, Young Adult

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

6

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13046)
Medical Research Council (MC_U106179471)
Medical Research Council (MC_U106179472)
This work was supported by the Medical Research Council [U106179472; MC_U106179472; U106179471; MC_U106179471] and the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981 to 23andMe)