Genome-wide Association Study of the Postprandial Triglyceride Response Yields Common Genetic Variation in Hepatic Lipase ().
Citations
Altmetric:
Series / Report no.
Open Access
Type
Article
Language
en
Date
2020-06-30
Research Projects
Organizational Units
Journal Issue
Title
Genome-wide Association Study of the Postprandial Triglyceride Response Yields Common Genetic Variation in Hepatic Lipase ().
Translated Title
Published in
Circ Genom Precis Med 2020; 13(4):e002693
Abstract
Background - The increase in serum triglyceride (TG) concentrations in response to a meal is considered a risk factor for cardiovascular disease. We aimed to elucidate the genetics of the postprandial TG response through genome-wide association studies (GWAS). Methods - Participants of the Netherlands Epidemiology of Obesity (NEO) study (n=5,630) consumed a liquid mixed meal after an overnight fast. GWAS of fasting and postprandial serum TG at 150 minutes were performed. To identify genetic variation of postprandial TG independent of fasting TG, we calculated the TG response at 150 min by the residuals of a nonlinear regression that predicted TG at 150 min as a function of fasting TG. Association analyses were adjusted for age, sex and principal components in a linear regression model. Next, using as rs7350789-A as a determinant, we performed linear regression analyses on the residuals of the postprandial response of 149 nuclear magnetic resonance (NMR) based metabolite measures. Results - GWAS of fasting TG and postprandial serum TG at 150 min resulted in completely overlapping loci, replicating previous GWAS. From GWAS of the TG response, we identified rs7350789-A (allele frequency=0.36), mapping to hepatic lipase (LIPC), to be associated with a smaller increase in TG concentrations at 150 min (beta= -0.11; p-value=5.1x10-8). GWAS of fasting and postprandial serum TG at 150 minutes were performed. Rs7350789-A was associated with responses of 33 metabolite measures (p-value<1.4x10-3), mainly smaller increases of the TG component in almost all high-density lipoprotein (HDL) sub-particles (HDL-TG), a smaller decrease of HDL diameter and smaller increases of most components of very low density lipoproteins (VLDL) sub-particles. Conclusions - GWAS of the TG response identified a variant near LIPC as a main contributor to postprandial TG metabolism independent of fasting TG concentrations, resulting in smaller increases of HDL-TG and VLDL sub-particles.