FOUR genes with significant effects on the timing of menopause have been uncovered by a recent study offering insights into reproductive aging and cancer risks. The study, led by the MRC Institute of Metabolic Science, University of Cambridge, UK, and The University of Exeter, UK, focused on the impact of rare genetic variants in ETAA1, ZNF518A, PNPLA8, and PALB2. Women with only one working copy of these genes tend to experience menopause between two and five-and-a-half years earlier than average.
The analysis used genetic data from over 106,000 post-menopausal women in the UK Biobank study. Researchers found that these rare variants cause a loss of protein function, affecting the genetic integrity of eggs. When DNA damage in eggs remains unrepaired, they die, influencing the timing of menopause. ZNF518A showed the strongest effect, with variants found in only 1 in 4,000 women, dramatically shortening reproductive lifespan compared to previously known genetic factors.
Anna Murray from the University of Exeter Medical School emphasised the impact of menopause timing on women’s lives, noting that understanding the underlying genetic changes could lead to future treatments that extend reproductive life. The study also found links between menopause timing and cancer risk, with the BRCA1 and BRCA2 genes, previously known for their role in cancer, also associated with earlier menopause.
Overall, the research highlights the broader implications of studying ovarian aging. John Perry from the University of Cambridge explained that this research advances our understanding of how the aging process in ovaries may contribute to DNA damage and cancer risk in general. Findings from the 100,000 Genomes Project also suggest that genetic variants tied to early menopause may influence new DNA changes passed on to future generations.
Abigail Craig, EMJ
Reference
Stankovic S et al. Genetic links between ovarian ageing, cancer risk and de novo mutation rates. Nature. 2024;633(8030):608-14.
