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
Year: 2019
Type: article
Study design: Observational Study
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 3344 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 standard deviations (SD) (95% confidence interval (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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddz015
Institutions: University of Exeter, University of Bristol, MRC Integrative Epidemiology Unit, Brigham and Women's Hospital, Harvard University, University of Massachusetts Amherst, Institute of Cancer Research, University of North Carolina at Chapel Hill, National Institute of Environmental Health Sciences, National Institutes of Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, University Hospitals Bristol NHS Foundation Trust, National Institute for Health and Care Research, NIHR Bristol Biomedical Research Centre
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Breast Cancer Now, Wellcome Trust, University Hospitals Bristol NHS Foundation Trust, NIHR Bristol Biomedical Research Centre, National Institute for Health and Care Research, British Heart Foundation, Institute of Cancer Research, University of Exeter, University of Bristol, National Institutes of Health, Roche Diagnostics, Medical Research Council, National Cancer Institute
Awards: Understanding the role of fatty acids in the aetiology of cardiovascular disease using novel causal inference methods, G1192034430, Reproductive and cardio-metabolic health, G151562090, G1605161196, NIHR Senior Investigator Award, G2214254730, Biochemical Markers in the nurses' Health Study Cohort, G2786058305, G294025628, G34112852, G3602225402, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3831911591, The NYU Women's Health Study, G4028681359, G4095281385, G4376790518, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G459566519, Obstetric, lifestyle and genetic determinants of atherosclerosis, fat mass, insulin, glucose and lipid levels in women in early middle age, G479225836, G4928840855, G519761550, G5260012927, G5562631338, G6175859254, G6200764915, G6249003666, G6689231961, G7095874527, G7194418384, G7407801207, Biochemical Markers in the Nurses? Health Study Cohort, G801210579, Premenopausal Hormone Levels and Risk of Breast Cancer, G8502142660, G8789231540, G8793412166, G926566425
OpenAlex ID: W2902650905