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The following is a summary of “Dissecting the shared genetic architecture between anti-Müllerian hormone and age at menopause based on genome-wide association study,” published in the December 2024 issue of Obstetrics and Gynecology by Long et al.     

Anti-Müllerian hormone (AMH) is widely studied for its association with menopause timing. Still, the role in predicting the onset of menopause remains controversial, with a limited understanding of the genetic and causal relationships between the 2 traits.  

Researchers conducted a retrospective study to investigate the shared genetic architecture and causal relationships between AMH and age at menopause (AAM).  

They used genome-wide association study (GWAS) summary statistics for AMH, N=7,049, and AAM, N=201,323, in people of European descent. The genetic association was analyzed using linkage disequilibrium score regression, pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation of Genetic Associations (FUMA), multimarker analysis of GenoMic annotation (MAGMA), and colocalization analysis. Tissue enrichment analysis utilized Genotype-Tissue Expression (GTEx) data and relationships were explored using Mendelian randomization (MR) and metabolite-mediated analysis.  

The results showed a positive genetic correlation between AMH and AAM, with a correlation coefficient of 0.88 (P=1.33×10^-5), 42 significant pleiotropic loci, including 10 loci (e.g., rs10734411, rs61913600, rs2277339) with colocalized effects were identified. The multimarker analysis revealed that 245 pleiotropic genes and genetic associations were enriched in whole blood, brain, liver, and kidneys. The MR identified 9 genes with potential causative effects on AMH and AAM. Additionally, 2-sample MR suggested that AAM may causally affect AMH, with very-low-density lipoprotein (VLDL) identified as a potential mediator.  

They concluded that AMH and AAM share a genetic architecture, indicating the need for multifactorial approaches to predict menopause and suggesting potential therapeutic targets to improve reproductive health outcomes.  

Source: ajog.org/article/S0002-9378(24)00744-0/fulltext