Genetic and Environmental Contributions to the Covariation Between Cardiometabolic Traits

J Am Heart Assoc. 2018 Apr 18;7(9):e007806. doi: 10.1161/JAHA.117.007806.

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), twin-based 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.

Keywords: biomarker; cardiac metabolism; environment; genes; heritability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Diseases in Twins / genetics*
  • Diseases in Twins / metabolism
  • Diseases in Twins / physiopathology
  • Energy Metabolism / genetics*
  • Female
  • Gene-Environment Interaction*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Heart Diseases / genetics*
  • Heart Diseases / metabolism
  • Heart Diseases / physiopathology
  • Heredity
  • Humans
  • Male
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Models, Genetic
  • Myocardium / metabolism*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Registries
  • Risk Assessment
  • Risk Factors
  • Sweden

Substances

  • Genetic Markers