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

Bénédicte L Tremblay; Frédéric Guénard; Benoît Lamarche; Louis Pérusse; Marie-Claude Vohl

doi:10.1016/j.nutres.2018.10.003

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

Nutr Res. 2019 Jan:61:22-30. doi: 10.1016/j.nutres.2018.10.003. Epub 2018 Oct 13.

Authors

Bénédicte L Tremblay¹, Frédéric Guénard², Benoît Lamarche³, Louis Pérusse⁴, Marie-Claude Vohl⁵

Affiliations

¹ Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 Hochelaga Blvd, Quebec City, QC, G1V 0A6, Canada. Electronic address: benedicte-l.tremblay.1@ulaval.ca.
² Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 Hochelaga Blvd, Quebec City, QC, G1V 0A6, Canada. Electronic address: frederic.guenard@fsaa.ulaval.ca.
³ Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 Hochelaga Blvd, Quebec City, QC, G1V 0A6, Canada. Electronic address: benoit.lamarche@fsaa.ulaval.ca.
⁴ Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 Hochelaga Blvd, Quebec City, QC, G1V 0A6, Canada; CHU de Québec Research Center - Endocrinology and Nephrology, 2705 Laurier Blvd, Quebec City, QC, G1V 4G2, Canada. Electronic address: louis.perusse@kin.ulaval.ca.
⁵ Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 Hochelaga Blvd, Quebec City, QC, G1V 0A6, Canada; CHU de Québec Research Center - Endocrinology and Nephrology, 2705 Laurier Blvd, Quebec City, QC, G1V 4G2, Canada. Electronic address: marie-claude.vohl@fsaa.ulaval.ca.

PMID: 30683436
DOI: 10.1016/j.nutres.2018.10.003

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 C36:4, serotonin, lysophosphatidylcholine acyl C20:4, citrulline, asymmetric dimethylarginine, phosphatidylcholine acyl-alkyl C36:5) 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 C36:4, phosphatidylcholine acyl-alkyl C36:5, and serotonin had significant phenotypic correlations with CM risk factors. Citrulline had a positive genetic correlation with apolipoprotein B100, while phosphatidylcholine acyl-alkyl C36:5 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.

Keywords: Bivariate genetic analysis; Cardiometabolic risk factors; Familial resemblances; Human; Metabolomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Canada
Child
Environment*
Family*
Female
France / ethnology
Humans
Male
Metabolome*
Metabolomics
Middle Aged
Plasma / metabolism*
Quantitative Trait, Heritable*
Risk Factors