Dr Katherine Ruth is a Lecturer in Clinical and Biomedical Sciences in the Reproductive Genomics group (https://sites.exeter.ac.uk/reprogenomics/) at the University of Exeter. Awarded her PhD in January 2016, she has extensive experience of population-based study data including UK Biobank and of applying methods in statistical genetics and genetic epidemiology. She has been a lead analyst in the international reproductive genetics consortium ReproGen, resulting in insights into the genetic basis of reproductive ageing published in Nature and Nature Genetics. Current research interests include using genetics to investigate the biological mechanisms of menopause timing and menopausal symptoms and to test relationships between sex hormone exposures over life and health in postmenopausal women.

Insights from genome-wide analyses of female reproductive ageing

Ovarian reserve declines over female lifetime, with menopause marking the end of natural fertility. Menopause also affects health and wellbeing, with three-quarters of women experiencing vasomotor symptoms (e.g. hot flushes). In this talk, I will describe insights from our genome-wide association studies to investigate the genetic basis of both the timing of menopause and also the symptoms experienced by women at menopause. Our genome-wide analyses of menopause timing in 201,323 women, as part of the ReproGen consortium, identified 290 genetic signals. These results highlighted the role of DNA damage response processes across the lifespan, suggesting potential treatment targets for the maintenance of ovarian reserve, and revealing relationships with health and disease. More recently, using exome sequencing data in 106,973 women from UK Biobank, we have identified rare protein-coding variation in nine genes with large effects on menopause timing and providing further evidence of links to cancer susceptibility. Finally, using routinely-collected health data in UK Biobank, we have explored the genetic basis of menopausal vasomotor symptoms, implicating TACR3 a known drug-target, yet highlighting limitations in our current knowledge. Collectively, our genome-wide studies have advanced understanding of the biology and aetiology of menopause.