A meta-analysis of genome-wide association studies suggests that several genetic variants predict the timing of menopause in women, whereas newly discovered variants further suggest a link between such genetic mechanisms and human longevity, according to findings published in Menopause.
“Although previous genetic studies have sought to discover genetic variants associated with [age of menopause] in normally aging populations, or in premature menopause, our current analysis aims to discover additional genetic variants that are associated with [age of menopause] in women with familial longevity,” Harold Bae, PhD, of the College of Public Health and Human Sciences at Oregon State University in Corvallis, Oregon, and colleagues wrote in the study background. “It is encouraging that some genetic studies of [age of menopause] have noted associations with genes that have also been implicated in slower aging, such as DNA repair and immune function genes.”
In a meta-analysis of genome-wide association studies, Bae and colleagues assessed data from 1,286 women participating in the Long Life Family Study (mean age at menopause, 51 years), a study of longevity and healthy aging conducted between 2006 and 2009, and 3,151 women participating in the Framingham Heart Study, an ongoing, family-based longitudinal study designed to assess risk factors for cardiovascular disease (mean age at menopause, 51 years). DNA samples from women in both studies were genotyped. Researchers used Cox proportional hazard models to estimate the association between each single nucleotide polymorphism (SNP) and age of menopause.
In the meta-analysis, researchers found that only one SNP, rs16991615, that was previously associated with age of menopause reached genome-wide significance (HR = 0.74). Additionally, researchers found that 576 SNPs corresponded to 121 loci and included variants associated with higher risk for earlier menopause, as well as variants associated with delayed menopause. Of those, 19 showed consistent effects and reached genome-wide statistical significance in a previously published genome-wide association study, according to the researchers, with an additional 14 SNPs reaching a “nominal” level of significance in the previously published study. The researchers also identified several novel SNPs associated with age at menopause.
“This work provides additional replication of associations between genetic variants in MCM8, UIMC1, ZNF346, BRSK1 and TMEM224 and [age of menopause], and suggestive associations of new variants with [age of menopause],” the researchers wrote. “The findings provide further evidence for [a] genetic basis of [age of menopause]. In addition, the discovery of new variants in a study enriched of long-lived individuals suggests that there may be genetic mechanisms of [age of menopause] that are linked to human longevity.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.