Genetics of physiological dysregulation: findings from the long life family study using joint models.

ABSTRACT: Recently, Mahalanobis distance (D_M) was suggested as a statistical measure of physiological dysregulation in aging individuals. We constructed D_M variants using sets of biomarkers collected at the two visits of the Long Life Family Study (LLFS) and performed joint analyses of longitudinal observations of D_M and follow-up mortality in LLFS using joint models. We found that D_M is significantly associated with mortality (hazard ratio per standard deviation: 1.31 [1.16, 1.48] to 2.22 [1.84, 2.67]) after controlling for age and other covariates. GWAS of random intercepts and slopes of D_M estimated from joint models found a genome-wide significant SNP (rs12652543, p=7.2×10^-9) in the TRIO gene associated with the slope of D<

SUBMITTER: Arbeev KG 

PROVIDER: S-EPMC7185144 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature