A study identifies rare protein-coding variants associated with ovarian ageing and cancer risk. Using data from the UK Biobank, researchers found that genes such as ZNF518A, PNPLA8, and SAMHD1 have a significant impact on ovarian ageing, with effects five times larger than those of common variants. These genes are linked to reproductive lifespan and cancer susceptibility. For example, variants in ZNF518A are associated with earlier menopause and later menarche, while variants in SAMHD1 are linked to increased cancer risk. The study also found that common genetic variants associated with earlier ovarian ageing are linked to higher rates of de novo mutations in offspring. This suggests a potential role for DNA damage response genes in maintaining genetic integrity in germ cells. The study highlights the genetic links between age of menopause and cancer risk, and provides evidence of the biological mechanisms underlying ovarian ageing. The findings have implications for understanding reproductive health, fertility, and cancer risk. The study also shows that rare variants in genes involved in DNA damage repair are associated with increased risk of various cancers, including prostate cancer and mesothelioma. The study underscores the importance of genetic factors in reproductive ageing and cancer risk, and highlights the need for further research into the underlying biological mechanisms.A study identifies rare protein-coding variants associated with ovarian ageing and cancer risk. Using data from the UK Biobank, researchers found that genes such as ZNF518A, PNPLA8, and SAMHD1 have a significant impact on ovarian ageing, with effects five times larger than those of common variants. These genes are linked to reproductive lifespan and cancer susceptibility. For example, variants in ZNF518A are associated with earlier menopause and later menarche, while variants in SAMHD1 are linked to increased cancer risk. The study also found that common genetic variants associated with earlier ovarian ageing are linked to higher rates of de novo mutations in offspring. This suggests a potential role for DNA damage response genes in maintaining genetic integrity in germ cells. The study highlights the genetic links between age of menopause and cancer risk, and provides evidence of the biological mechanisms underlying ovarian ageing. The findings have implications for understanding reproductive health, fertility, and cancer risk. The study also shows that rare variants in genes involved in DNA damage repair are associated with increased risk of various cancers, including prostate cancer and mesothelioma. The study underscores the importance of genetic factors in reproductive ageing and cancer risk, and highlights the need for further research into the underlying biological mechanisms.