Kentistou K.A. Kaisinger L.R. Stankovic S. Vaudel M. Mendes de Oliveira E. Messina A. Walters R.G. Liu X. Busch A.S. Helgason H. et al. (2024) Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nature Genetics 56: 1397-1411.
View on Pub Med (38951643)Reproductive Lifespan
Variation in age at puberty and menopause is associated with a range of health outcomes including effects on fertility, endometriosis, cardiovascular disorders, osteoporosis, obesity, breast and ovarian cancer. Genetic studies demonstrate the complex nature of the variation associated with reproductive lifespan and relationships with these other conditions.
Age at puberty
The timing of puberty varies between individuals and is influenced by both rare and common variants (Day et al., 2017, 28436984; Gajbhiye et al., 2018, 30345074; Perry et al., 2014, 25231870). Rare mutations in genes that disrupt the development and function of the gonadotrophin-releasing hormone (GnRH) pathway, pituitary hormones, and their receptors can result in delayed timing or the absence of puberty. Mapping studies have implicated a diverse range of mechanisms in the regulation of puberty timing with enrichment of variants in or near genes disrupted in rare disorders of puberty and highlight shared etiological factors between puberty timing and metabolic disease outcomes (Day et al., 2017, 28436984, Kentistou et al., 2024, 38951643; Perry et al., 2014, 25231870).
Age at Menopause
Variation in age at menopause influences fertility and healthy ageing in women. Genetic determinants of ovarian ageing assessed using normal variation in age at natural menopause identified over 250 common variants associated with clinical extremes of age at natural menopause and implicate a broad range of DNA damage response processes (Day et al., 2015, 26414677; Perry et al., 2013, 23307926; Ruth et al., 2021, 34349265). Genetic variants associated with later age at menopause are also associated with improved bone health and reduced risk of type 2 diabetes but increase the risk of hormone-sensitive cancers.
References
2024
2023
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View on Pub Med (36914876)2021
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