A team of scientists has identified a variant in the sequence of the CCDC201 gene that, when inherited from both parents in a homozygous state, causes menopause to occur on average nine years earlier than usual. The company deCODE genetics, together with collaborators from Iceland, Denmark, the United Kingdom and Norway, have published a study in the journal Nature Genetics that reveals a rare genotype with a significant impact on women’s health.
The age of menopause has a great influence on fertility and the risk of developing certain diseases, especially what is known as premature menopause, which is the cessation of ovulation before a woman turns 40, and which can have important consequences on health and emotional well-being.
A gene that affects female reproductive health
This research focused on recessive models, that is, individuals with two copies of a genetic variant (homozygotes), which are less studied compared to the additive model, which focuses mainly on individuals with only one copy of a genetic variant, especially when it is rare.
Analyzing data from 174,329 women from Iceland, Denmark, the United Kingdom and Norway, researchers identified a variant that causes a protein disruption, changing an Arginine at position 162 to a termination in the CCDC201 gene, which significantly impacts age of onset of menopause (AOM).
The CCDC201 gene, identified as a protein-coding gene in humans in 2022, has been shown to be highly expressed in egg cells, and this study shows that its complete loss of function significantly impacts female reproductive health.
Women who carry two copies of this variant, called homozygotes, experience menopause an average of nine years earlier than women who do not carry it. This homozygous genotype is found in about 1 in 10,000 women of Northern European descent, leading to primary ovarian failure, defined as menopause before age 40, in nearly half of carriers. As a result, these women have fewer children and rarely conceive after age 30.
This discovery highlights the importance of considering diverse genetic models to understand diseases such as primary ovarian failure. The study highlights the potential benefits of genetic counselling for women carrying this specific genotype. An early diagnosis allows for informed reproductive decisions and better management of symptoms associated with early menopause.
