Genetic links between ovarian ageing, cancer risk and de novo mutation rates.

ABSTRACT: Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing¹. Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility¹, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan-that is, earlier age at menopause (by 5.61 years) and later age at menarch

SUBMITTER: Stankovic S 

PROVIDER: S-EPMC11410666 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature