Changes to your DNA affect everything about you, from your appearance and behaviour to your risk of getting various diseases. But new research has discovered four genes which, if changed, can have a major impact on the age you’ll be when menopause hits.
The research, conducted by scientists at the University of Exeter, the University of Cambridge and the Wellcome Sanger Institute, also revealed genetic links between menopause age and cancer risk.
Genes come in pairs, and the researchers discovered that when women only have one working copy of the newly identified genes (known as ETAA1, ZNF518A, PNPLA8 and PALB2), their menopause age tends to be 2 to 5.5 years earlier than the average age (50 years old).
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“For decades, menopause has been under-researched, yet now this is a rapidly evolving area of science,” said study co-lead Professor Anna Murray, of the University of Exeter Medical School.
“The timing of menopause has a huge impact on women as they plan their careers and lives, and understanding the genetic changes is of particular interest in terms of potential treatments that could prolong reproductive life in future.”
Published in Nature, the study analysed the data of 106,973 post-menopausal female participants in the UK Biobank study, as the scientists searched for changes in these genes.
Such genetic changes are rare, but they have a five-times greater impact on menopause age than more common changes. In particular, changes to the ZNF518A had the strongest impact on shortening reproductive lifespan – but these variants are only found in 1 in 4,000 women.
So how do they bring menopause forward? These genetic changes can damage the DNA in eggs, which may then die – and a woman’s rate of egg loss determines her menopausal age.
These genetic changes don’t just teach us more about menopause, but also highlight the risk of disease. In this study, the scientists discovered that the DNA damage in genes associated with early menopause was also linked to cancer risk, including changes in the BRCA1 and BRCA2 genes.
What’s more, changes to a different gene, SAMHD1, actually made menopause happen roughly one year later than average – and was also linked to increased cancer risk.
"Ovaries are powerful architects of overall health in women, not just reproductive health," paper author Dr Staša Stanković, part of senior author Prof John Perry's research team, told BBC Science Focus. "As we learn more about mechanisms that regulate ovarian function, we not only unlock biological insights behind infertility and other reproductive disorders but shed light on shared biology that predisposes women to other conditions."
She added: "A better understanding of the processes involved in ovarian ageing also improves our ability to predict age at menopause, as well as developing potential novel therapeutics for ovary-centric conditions."
The team also discovered that these changes in mothers’ DNA lead to more changes in the DNA they pass on to their children.
“Until now, we knew very little about what influences these new DNA changes, apart from parental age,” said Dr Hilary Martin, a study co-lead from the Wellcome Sanger Institute. “This is the first time we’ve seen that existing common variation in DNA influences the rate of these changes.”
About our expert
Dr Staša Stanković is a reproductive geneticist with a PhD in Reproductive Genomics from the University of Cambridge. Her research has appeared in journals Nature Medicine, Nature, Nature Genetics, and Cell Genomics.
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