Perry, J. R.B., McMahon, G., Day, F. R., Ring, S. M., Nelson, S. M. and Lawlor, D. A. (2016) Genome-wide association study identifies common and low-frequency variants at the AMHgene locus that strongly predict serum AMH levels in males. Human Molecular Genetics, 25(2), pp. 382-388. (doi: 10.1093/hmg/ddv465) (PMID:26604150) (PMCID:PMC4706112)
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Abstract
Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adolescents aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ∼9 M ‘1000 Genomes Reference Panel’ imputed genetic variants. Genetic variants at the AMH protein-coding gene showed considerable allelic heterogeneity, with both common variants [rs4807216 (PMale = 2 × 10−49, Beta: ∼0.9 SDs per allele), rs8112524 (PMale = 3 × 10−8, Beta: ∼0.25)] and low-frequency variants [rs2385821 (PMale = 6 × 10−31, Beta: ∼1.2, frequency 3.6%)] independently associated with apparently large effect sizes in males, but not females. For all three SNPs, we highlight mechanistic links to AMH gene function and demonstrate highly significant sex interactions (PHet 0.0003–6.3 × 10−12), culminating in contrasting estimates of trait variance explained (24.5% in males versus 0.8% in females). Using these SNPs as a genetic proxy for AMH levels, we found no evidence in additional datasets to support a biological role for AMH in complex traits and diseases in men.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Nelson, Professor Scott |
Authors: | Perry, J. R.B., McMahon, G., Day, F. R., Ring, S. M., Nelson, S. M., and Lawlor, D. A. |
College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
Journal Name: | Human Molecular Genetics |
Publisher: | Oxford University Press |
ISSN: | 0964-6906 |
ISSN (Online): | 1460-2083 |
Published Online: | 24 November 2015 |
Copyright Holders: | Copyright © 2015 The Authors |
First Published: | First published in Human Molecular Genetics 25(2):382-388 |
Publisher Policy: | Reproduced under a Creative Commons License |
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