| 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 |
| Journal: | Human Molecular Genetics |
| Published: | 14 Jan 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30649302/ |
| DOI: | https://doi.org/10.1093/hmg/ddz015 |
| URL: | https://europepmc.org/articles/pmc6452199?pdf=render |
| Citations: | 24 (8 in last 2 years) as of 8 Aug 2024 |
Publication 12014
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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.</p>
15 Authors
- Katherine S Ruth
- Ana Luiza G Soares
- Maria-Carolina Borges
- A Heather Eliassen
- Susan E Hankinson
- Michael E Jones
- Peter Kraft
- Hazel B Nichols
- Dale P Sandler
- Minouk J Schoemaker
- Jack A Taylor
- Anne Zeleniuch-Jacquotte
- Deborah A Lawlor
- Anthony J Swerdlow
- Anna Murray
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