GENETIC INFLUENCE ON AGE OF MENOPAUSE IN LONG-LIVED INDIVIDUALS

ABSTRACT: Abstract Several studies have observed that women who are able to naturally have children later in life tend to live longer. We hypothesize that the evolutionary pressure to extend the period of time in which women can bear children and therefore have the opportunity to have more of them could be a mechanism for the selection of genetic variants that slow aging and decrease risk for age-related diseases. We performed a genome-wide association study (GWAS) for age of menopause (AOM) in 1,317 women in the Long Life Family Study (LLFS), using approximately 1.5M single nucleotide polymorphisms (SNP). We used Cox proportional hazard regression to model AOM accounting for censoring of 1,127 women, with a robust variance estimator to adjust for within familial relations. No SNP reached genome-wide significance, but SNPs rs10957156 (p=0.00043) in CHD7, rs4886238 (p=0.00051) in TDRD3, rs16991615 (p=0.00080) in MCM8, rs16858210 (p=0.013) in PARL/POLR2H, rs11668344 (p=0.033) in BRSK1, and rs8070740 (p=0.036) in RPAIN previously associated with AOM replicated in the LLFS GWAS. Several top SNPs in the LLFS (p<10^-4) also replicated the results in a large meta-analysis of AOM published in 2015. Among these, rs10239340 is a significant expression quantitative loci (eQTL) of IRF5, a gene whose function is involved in promotion and inhibition of inflammation, in multiple tissue types. Additionally, rs10455038 is a significant eQTL of PPIC, which participates in many biological processes such as metabolism, apoptosis, redox, and inflammation. This study is the first GWAS of AOM in a sample enriched for longevity.

SUBMITTER: Bae H 

PROVIDER: S-EPMC6184344 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature