Dissecting the shared genetic architecture between anti-Müllerian hormone and age at menopause based on genome-wide association study
Long, Panpan et al. (American Journal of Obstetrics & Gynecology, Volume 231, Issue 6, 634.e1 – 634.e11) aimed to explore the shared genetic architecture between anti-Müllerian hormone and age at menopause, to identify shared pleiotropic loci and genes, and to investigate causal association and potential causal mediators.
Using summary statistics from publicly available genome-wide association studies on anti-Müllerian hormone (N=7049) and age at menopause (N=201,323) in Europeans, they investigated the global genetic architecture between anti-Müllerian hormone and age at menopause through linkage disequilibrium score regression.
A positive genetic association (correlation coefficient=0.88, P=1.33×10−5) was observed between anti-Müllerian hormone and age at menopause. By using pleiotropic analysis under composite null hypothesis and Functional Mapping and Annotation of Genetic Associations, 42 significant pleiotropic loci were identified that were associated with anti-Müllerian hormone and age at menopause, and 10 of these had colocalized loci.
Additionally, 245 significant pleiotropic genes were identified by multimarker analysis of GenoMic annotation. Genetic associations between anti-Müllerian hormone and age at menopause were markedly concentrated in various tissues including whole blood, brain, heart, liver, muscle, pancreas, and kidneys. Further, summary data-based Mendelian randomization analysis revealed 9 genes that may have a causative effect on both anti-Müllerian hormone and age at menopause. A potential causal effect of age at menopause on anti-Müllerian hormone was suggested by 2-sample Mendelian randomization analysis, with very-low-density lipoprotein identified as a potential mediator.
Conclusion
This study revealed a shared genetic architecture between anti-Müllerian hormone and age at menopause, providing a basis for experimental investigations and individual therapies to enhance reproductive outcomes. Furthermore, their findings emphasized that relying solely on anti-Müllerian hormone is not sufficient for accurately predicting the age at menopause, and a combination of other factors needs to be considered, which may result in exploring new therapeutics aimed at delaying at the onset of menopause.