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Type: Journal article
Title: Genome-wide association study identifies common and low-frequency variants at the AMH gene locus that strongly predict serum AMH levels in males
Author: Perry, J.
McMahon, G.
Day, F.
Ring, S.
Nelson, S.
Lawlor, D.
Citation: Human Molecular Genetics, 2016; 25(2):382-388
Publisher: Oxford University Press
Issue Date: 2016
ISSN: 0964-6906
Statement of
John R.B. Perry, George McMahon, Felix R. Day, Susan M Ring, Scott M. Nelson, Debbie A. Lawlor
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 (P(Male) = 2 × 10(-49), Beta: ∼0.9 SDs per allele), rs8112524 (P(Male) = 3 × 10(-8), Beta: ∼0.25)] and low-frequency variants [rs2385821 (P(Male) = 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 (P(Het) 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.
Keywords: Genes; single nucleotide polymorphism; genetics mullerian-inhibiting hormone; genome-wide association study
Rights: © The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/hmg/ddv465
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