News | Menopause Nine Years Earlier: Potential Reproductive Impact of a CCDC201 Variant



News | Menopause Nine Years Earlier: Potential Reproductive Impact of a CCDC201 Variant


Scientists at deCODE genetics and their collaborators recently published a study in Nature Genetics identifying a rare genotype with a significant effect on women's health. Women who inherit a particular CCDC201 sequence variant from both parents experience menopause an average of nine years earlier than noncarriers.


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The study was conducted by deCODE genetics, an Amgen subsidiary, and researchers from Iceland, Denmark, the United Kingdom, and Norway. Age at menopause affects fertility and disease risk. The study used a recessive model, examining people with two copies of the same sequence variant. This approach is less common than additive models that usually examine one copy, particularly when the variant itself is rare.


After analyzing data from more than 174,000 women across the four countries, researchers identified a stop-gain variant that changes arginine at position 162 of CCDC201 into a stop codon. The variant significantly affects age at menopause (AOM). CCDC201 was recognized as a human protein-coding gene only in 2022 and is highly expressed in oocytes. The study indicates that complete loss of its function substantially affects female reproductive health.


Women carrying two copies of the variant, known as homozygotes, experience menopause an average of nine years earlier than noncarriers. The genotype occurs in about 1 in 10,000 Northern European women. Nearly half of carriers experience menopause before age 40, meeting the definition of primary ovarian insufficiency. Their fertility is therefore markedly reduced, and childbirth after age 30 is uncommon.


The finding underscores the importance of considering several genetic models when studying conditions such as primary ovarian insufficiency. It also highlights the potential value of genetic counseling for women with this genotype. Early diagnosis may support informed reproductive decisions and management of symptoms related to early menopause.


Source:

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