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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Age at menopause AOM has a substantial impact on fertility and disease risk.
While many loci with variants that associate with AOM have been identified through genome-wide association studies GWAS under an additive model, other genetic models are rarely considered 1. The genotype is present in one in 10, northern European women and leads to primary ovarian insufficiency in close to half of them. The CCDC gene was only found in humans in and is highly expressed in oocytes. Homozygosity for CCDC loss-of-function has a substantial impact on female reproductive health, and homozygotes would benefit from reproductive counseling and treatment for symptoms of early menopause.
Menopause is caused by the depletion of the primordial follicle pool. It is estimated that natural fertility ends on average 10 years before menopause 3 , 5. EM and POI are a well-known cause of infertility, which is increasingly relevant as women in many populations are choosing to have children later in life 3.
Through genome-wide association studies GWAS , we and others have reported associations of rare and low-frequency variants with variation in AOM, mostly under an additive model 6 , 7 , 8. Rare variants in several genes have also been reported to cause Mendelian forms of POI 9 although many are only reported in a small number of cases or in single families 4 , Despite advances in understanding the genetic causes of EM and POI, genetic screening has mainly been focused on Turner syndrome, which has a prevalence of 1 in 2,, and the FMR1 premutation, found in 1 in 8, women 4 , We tested Known genes are shown in the plot.
