Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency.

ABSTRACT: 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 considered¹. Here through GWAS meta-analysis under the recessive model of 174,329 postmenopausal women from Iceland, Denmark, the United Kingdom (UK; UK Biobank) and Norway, we study low-frequency variants with a large effect on AOM. We discovered that women homozygous for the stop-gain variant rs117316434 (A) in CCDC201 (p.(Arg162Ter), minor allele frequency ~1%) reached menopause 9 years earlier than other women (P = 1.3 × 10^-15). The genotype is present in one in 10,000 northern European women and leads to prima

SUBMITTER: Oddsson A 

PROVIDER: S-EPMC11387189 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature