dc.contributor.author | Ruth, KS | |
dc.contributor.author | Soares, ALG | |
dc.contributor.author | Borges, M-C | |
dc.contributor.author | Eliassen, AH | |
dc.contributor.author | Hankinson, SE | |
dc.contributor.author | Jones, ME | |
dc.contributor.author | Kraft, P | |
dc.contributor.author | Nichols, HB | |
dc.contributor.author | Sandler, DP | |
dc.contributor.author | Schoemaker, MJ | |
dc.contributor.author | taylor, JA | |
dc.contributor.author | Zeleniuch-Jacquotte, A | |
dc.contributor.author | Lawlor, DA | |
dc.contributor.author | Swerdlow, AJ | |
dc.contributor.author | Murray, A | |
dc.date.accessioned | 2019-01-16T12:03:25Z | |
dc.date.issued | 2019-01-14 | |
dc.description.abstract | Anti-Müllerian hormone (AMH) is required for sexual differentiation in the fetus, and in adult females AMH is produced by growing ovarian follicles. Consequently, AMH levels are correlated with ovarian reserve, declining towards menopause when the oocyte pool is exhausted. A previous genome-wide association study identified three genetic variants in and around the AMH gene that explained 25% of variation in AMH levels in adolescent males but did not identify any genetic associations reaching genome-wide significance in adolescent females. To explore the role of genetic variation in determining AMH levels in women of late reproductive age, we carried out a genome-wide meta-analysis in 3,344 pre-menopausal women from five cohorts (median age 44–48 years at blood draw). A single genetic variant, rs16991615, previously associated with age at menopause, reached genome-wide significance at P=3.48×10-10, with a per allele difference in age-adjusted inverse normal AMH of 0.26 SD (95% CI [0.18,0.34]). We investigated whether genetic determinants of female reproductive lifespan were more generally associated with pre-menopausal AMH levels. Genetically-predicted age at menarche had no robust association but genetically-predicted age at menopause was associated with lower AMH levels by 0.18 SD (95% CI [0.14,0.21]) in age-adjusted inverse normal AMH per one-year earlier age at menopause. Our findings provide genetic support for the well-established use of AMH as a marker of ovarian reserve. | en_GB |
dc.description.sponsorship | Breast Cancer Now | en_GB |
dc.description.sponsorship | Institute of Cancer Research | en_GB |
dc.identifier.citation | Published online 14 January 2019. | en_GB |
dc.identifier.doi | 10.1093/hmg/ddz015 | |
dc.identifier.uri | http://hdl.handle.net/10871/35479 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press (OUP) | en_GB |
dc.rights.embargoreason | Under embargo until 14 January 2021 in compliance with publisher policy. | |
dc.rights | © The Author(s) 2019. Published by Oxford University Press. All rights reserved. | |
dc.subject | AMH | en_GB |
dc.subject | anti-mullerian hormone | en_GB |
dc.subject | genome-wide association study | en_GB |
dc.title | Genome-wide association study of anti-Müllerian hormone levels in pre-menopausal women of late reproductive age and relationship with genetic determinants of reproductive lifespan | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-16T12:03:25Z | |
dc.identifier.issn | 0964-6906 | |
dc.description | This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record. | en_GB |
dc.identifier.journal | Human Molecular Genetics | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2019-01-10 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2019-01-10 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-01-15T12:10:48Z | |
refterms.versionFCD | AM | |
refterms.panel | A | en_GB |