Genetic insights into biological mechanisms governing human ovarian ageing.

ABSTRACT: Reproductive longevity is essential for fertility and influences healthy ageing in women^1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations³. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonst

SUBMITTER: Ruth KS 

PROVIDER: S-EPMC7611832 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature