Genetic and environmental influences on serum oxylipins, endocannabinoids, bile acids and steroids

Abstract

Lipid bioactivity is a result of direct action and the action of lipid mediators including oxylipins, endocannabinoids, bile acids and steroids. Understanding the factors contributing to biological variation in lipid mediators may inform future approaches to understand and treat complex metabolic diseases. This research aims to determine the contribution of genetic and environmental influences on lipid mediators involved in the regulation of inflammation and energy metabolism. This study recruited 138 monozygotic (MZ) and dizygotic (DZ) twins aged 18-65 years and measured serum oxylipins, endocannabinoids, bile acids and steroids using liquid chromatography mass-spectrometry (LC-MS). In this classic twin design, the similarities and differences between MZ and DZ twins are modelled to estimate the contribution of genetic and environmental influences to variation in lipid mediators. Heritable lipid mediators included the 12-lipoxygenase products 12-hydroxyeicosatetraenoic acid [0.70 (95% CI: 0.12,0.82)], 12-hydroxyeicosatetraenoic acid [0.73 (95% CI: 0.30,0.83)] and 14-hydroxydocosahexaenoic acid [0.51 (95% CI: 0.07,0.71)], along with the endocannabinoid docosahexaenoylethanolamide [0.52 (95% CI: 0.15,0.72)]. For others such as 13-hydroxyoctadecatrienoic acid and lithocholic acid the contribution of environment to variation was stronger. With increased understanding of lipid mediator functions in health, it is important to understand the factors contributing to their variance. This study provides a comprehensive analysis of lipid mediators and extends pre-existing knowledge of the genetic and environmental influences on the human lipidome.

Heritability of Urinary Amines, Organic Acids, and Steroid Hormones in Children

“…In this same sample of twins, it was shown that 20% of the urinary NMR metabolomic profile was stable over a 2-month period and that both common genetic and shared environmental factors contribute to the short-term stability of the urinary metabolome in adults [49]. Previous studies investigating the blood metabolome in adult populations [8,10–13], also obtained very limited evidence for contributions of the common environment, while the influence of genetics is substantial. To date, genome-wide association studies for blood metabolites have identified more than 800 metabolite loci, with an average heritability of metabolite loci of 6% for lipids and lipid-like molecules and of 1% for organic acids and derivatives [18].…”

“…Previous heritability studies of metabolomics data in various biofluids found that about 50% of the variance in metabolite levels is due to additive genetic factors [6,7]. Non-additive (i.e., dominant genetic effects) and common (shared) environmental factors (i.e., shared by family members) generally have a minor influence on metabolite levels [8][9][10][11][12][13]. Some nuance on the contribution of genetic factors is possible: the contribution to individual differences in metabolite levels differs per metabolite class and subclass, with generally somewhat higher heritability estimates observed for lipids and lipid-like molecules than for organic acids and derivatives [14][15][16][17][18][19][20][21].…”

Heritability of Urinary Amines, Organic Acids, and Steroid Hormones in Children

“…In this same sample of twins, it was shown that 20% of the urinary NMR metabolomic profile was stable over a 2-month period and that both common genetic and shared environmental factors contribute to the short-term stability of the urinary metabolome in adults [52]. Previous studies investigating the blood metabolome in adult populations [8,[10][11][12][13]] also obtained very limited evidence for contributions of the common environment, whereas the influence of genetics is substantial. To date, genome-wide association studies for blood metabolites have identified more than 800 metabolite loci, with an average heritability of metabolite loci of 6% for lipids and lipid-like molecules and of 1% for organic acids and derivatives [18].…”

“…Previous heritability studies of metabolomics data in various biofluids found that about 50% of the variance in metabolite levels is due to additive genetic factors [6,7]. Nonadditive (i.e., dominant genetic effects) and common (shared) environmental factors (i.e., shared by family members) generally have a minor influence on metabolite levels [8][9][10][11][12][13]. Some nuance on the contribution of genetic factors is possible: the contribution to individual differences in metabolite levels differs per metabolite class and subclass, with generally somewhat higher heritability estimates observed for lipids and lipid-like molecules than for organic acids and derivatives [14][15][16][17][18][19][20][21].…”

Genetic analyses of circulating PUFA-derived mediators identifies heritable dihydroxyeicosatrienoic acid species

“…Some PUFA species (e.g., AA, eicosadienoic acid, DHA, and EPA) have been subject to genetic analyses, and 12%− 59% of the variance in the blood levels of those fatty acid studied to-date has been estimated to be due to genetic factors [28,29]. Recent studies have started the systematic genetic characterisation of PUFA-derived oxygenated mediator derivatives [30][31][32].…”