Familial resemblances in human plasma metabolites are attributable to both genetic and common environmental effects.

ABSTRACT

Metabolites are of great importance for understanding the pathogenesis of several diseases. Understanding the genetic contribution to metabolite concentrations may provide insights into mechanisms of complex diseases. Several studies have investigated heritability of metabolites but none investigated potential influences of genetic and environmental factors on the relationship between metabolites and cardiometabolic (CM) risk factors. Thus, we tested the hypothesis that both genetic and common environmental effects contribute to the variance of plasma metabolite concentrations and that shared genetic and environmental effects explain their phenotypic correlations with CM risk factors. To test this hypothesis, variance component method and bivariate genetic analysis were performed in a family-based sample of 48 French Canadians from 16 families. Familial resemblances were computed for all 147 detected metabolites and 9 (acetylornithine, acylcarnitine C9, arginine, phosphatidylcholine acyl-alkyl C364, serotonin, lysophosphatidylcholine acyl C204, citrulline, asymmetric dimethylarginine, phosphatidylcholine acyl-alkyl C365) showed a significant familial effect (55.7%, 18.7%, and 37.0% for maximal heritability, genetic heritability, and common environmental effect, respectively). Citrulline, phosphatidylcholine acyl-alkyl C364, phosphatidylcholine acyl-alkyl C365, and serotonin had significant phenotypic correlations with CM risk factors. Citrulline had a positive genetic correlation with apolipoprotein B100, while phosphatidylcholine acyl-alkyl C365 had a positive environmental correlation with total cholesterol. In conclusion, familial resemblances in metabolite concentrations were mainly attributable to common environmental effect when considering metabolites with a significant familial effect. Common genetic and environmental factors may also influence the relationship between metabolites and CM risk factors.