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dc.contributor.authorPerry, Johnen
dc.contributor.authorMcMahon, Georgeen
dc.contributor.authorDay, Felixen
dc.contributor.authorRing, Susan Men
dc.contributor.authorNelson, Scott Men
dc.contributor.authorLawlor, Debbie Aen
dc.date.accessioned2015-11-16T13:58:24Z
dc.date.available2015-11-16T13:58:24Z
dc.date.issued2015-11-24en
dc.identifier.citationPerry et al. Human Molecular Genetics (2015) Vol. 25, Issue 2, pp. 382-388. doi: 10.1093/hmg/ddv465en
dc.identifier.issn0964-6906
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252617
dc.description.abstractAnti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the fetus 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 characterised. In samples from 2815 children aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ~9M ‘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=2x10⁻⁴⁹, Beta: ~0.9 SDs per allele], rs8112524 [PMale=3x10⁻⁸, Beta: ~0.25]) and low-frequency variants (rs2385821 [PMale=6x10⁻³¹, 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 to 6.3x10⁻¹²), culminating in contrasting estimates of trait variance explained (24.5% in males vs 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.
dc.description.sponsorshipThe UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The work in this paper is funded by a grant from the US National Institute of Health (R01 DK077659). DAL, SMR and GM work in a Unit that receives funds from the UK Medical Research Council (MC_UU_12013/5) and the University of Bristol. DAL is a UK NIHR Senior Investigator (NF-SI-0611-10196).
dc.languageEnglishen
dc.language.isoenen
dc.publisherOxford University Press
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.titleGenome-wide association study identifies common and low-frequency variants at the AMH gene locus that strongly predict serum AMH levels in malesen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/hmg/ddv465en
prism.endingPage388
prism.publicationDate2015en
prism.publicationNameHuman Molecular Geneticsen
prism.startingPage382
prism.volume25en
dc.rioxxterms.funderMRC
dc.rioxxterms.funderNIHR
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderNIH
dc.rioxxterms.projectid102215/2/13/2
dc.rioxxterms.projectidR01 DK077659
dc.rioxxterms.projectidMC_UU_12013/5
dc.rioxxterms.projectidNF-SI-0611-10196
dcterms.dateAccepted2015-11-09en
rioxxterms.versionofrecord10.1093/hmg/ddv465en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-11-24en
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.contributor.orcidDay, Felix [0000-0003-3789-7651]
dc.identifier.eissn1460-2083
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idWellcome Trust (091310/Z/10/Z)
pubs.funder-project-idMedical Research Council (MC_U106179472)
cam.orpheus.successThu Jan 30 12:55:34 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2300-01-01


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales