Genetic and environmental contributions to the covariation between cardiometabolic traits

Abstract

Background--The variation and covariation for many cardiometabolic traits have been decomposed into genetic and environmental fractions, by using twin or single-nucleotide polymorphism (SNP) models. However, differences in population, age, sex, and other factors hamper the comparison between twin- and SNP-based estimates. Methods and Results--Twenty-four cardiometabolic traits and 700,000 genotyped SNPs were available in the study base of 10 682 twins from TwinGene cohort. For the 27 highly correlated pairs (absolute phenotypic correlation coefficient ≥0.40), twinbased bivariate structural equation models were performed in 3870 complete twin pairs, and SNP-based bivariate genomic relatedness matrix restricted maximum likelihood methods were performed in 5779 unrelated individuals. In twin models, the model including additive genetic variance and unique/nonshared environmental variance was the best-fitted model for 7 pairs (5 of them were between blood pressure traits); the model including additive genetic variance, common/shared environmental variance, and unique/nonshared environmental variance components was best fitted for 4 pairs, but estimates of shared environment were close to zero; and the model including additive genetic variance, dominant genetic variance, and unique/nonshared environmental variance was best fitted for 16 pairs, in which significant dominant genetic effects were identified for 13 pairs (including all 9 obesity-related pairs). However, SNP models did not identify significant estimates of dominant genetic effects for any pairs. In the paired t test, twin- and SNP-based estimates of additive genetic correlation were not significantly different (both were 0.67 on average), whereas the nonshared environmental correlations from these 2 models differed slightly from each other (on average, twin-based estimate=0.64 and SNP-based estimate=0.68). Conclusions--Beside additive genetic effects and nonshared environment, nonadditive genetic effects (dominance) also contribute to the covariation between certain cardiometabolic traits (especially for obesity-related pairs); contributions from the shared environment seem to be weak for their covariation in TwinGene samples.