A woman’s age at natural menopause (ANM) is a significant indicator of her overall health. Early or late ANM is linked to a number of negative consequences later in life. Despite the fact that it is an inheritable trait, its genetic determinant is still unknown. To better characterise the genetic architecture of ANM, researchers performed genome-wide association study (GWAS) meta-analyses in European and trans-ancestry samples using GWAS summary statistics from three large studies: the Reproductive Genetics Consortium, the UK Biobank cohort, and the BioBank Japan Project, followed by a series of bioinformatic assessments and futurism. This biggest meta-analysis found 49 new loci and 3 secondary signals related with ANM at the genome-wide significance level by combining the summary statistics from three GWAS with up to 225 200 individuals. At the majority of the linked loci, no demographic specificity or heterogeneity was identified. Functional annotations ranked 90 candidate genes at the newly discovered loci in order of importance. Hormone replacement treatment (HRT) was a causative link among the 26 characteristics that were genetically associated with ANM, indicating a causal pattern in which HRT was determined by ANM.
The results contributed to a better understanding of the genesis of female menopause and gave insight on potential novel treatments for aberrant menopause.