Scientists from deCODE genetics and their colleagues have identified a sequence variant in the CCDC201 Gene that, when inherited homozygously from both parents, causes menopause to occur on average nine years earlier.

deCODE genetics, a subsidiary of Amgen, and collaborators from Iceland, Denmark, the UK and Norway today published a study in Nature Genetics uncovering a rare genotype that has significant implications for women’s health.

Age at menopause significantly affects fertility and disease risk. This research focused on recessive models, or people with two copies of a sequence variant, known as homozygotes, which are less commonly studied than the additive model, which relies primarily on people carrying one copy of a sequence variant, especially when it is rare. By analyzing data from over 174,000 women in Iceland, Denmark, the United Kingdom, and Norway, the researchers discovered a stop-gain variant that results in a change of and arginine at position 162 to termination in the CCDC201 Gene that dramatically affects AOM.

The CCDC201 The gene was only identified as a protein-coding gene in humans in 2022 and has been highly expressed in egg cells since then. This study shows that its complete loss of function has significant implications for female reproductive health.

Women who carry two copies of this variant, known as homozygotes, experience menopause on average nine years earlier than non-carriers. This homozygous genotype occurs in about 1 in 10,000 women of northern European descent and leads to primary ovarian failure, defined as menopause before the age of 40, in almost half of carriers. As a result, women with this genotype have fewer children and very rarely have children after the age of 30.

This discovery underscores the importance of considering different genetic models to understand diseases such as primary ovarian insufficiency.

The study highlights the potential benefit of genetic counseling for women with this specific genotype. Early diagnosis enables informed decisions regarding reproductive behavior and treatment of symptoms associated with early menopause.