Genome-wide association study of the postprandial triglyceride response yields common genetic variation in LIPC (hepatic lipase)
| Autor: | Raymond Noordam, Diana van Heemst, Lisanne L. Blauw, Dorina Ibi, Ruifang Li-Gao, Tim Christen, Renée de Mutsert, Ko Willems van Dijk, J. Wouter Jukema, Jan B. van Klinken, Martijn E.T. Dollé, Dennis O. Mook-Kanamori, Frits R. Rosendaal, Stella Trompet, Patrick C.N. Rensen |
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| Přispěvatelé: | Laboratory Genetic Metabolic Diseases, Laboratory for General Clinical Chemistry, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Genome-wide association study Disease Biology Lipoproteins VLDL Polymorphism Single Nucleotide Genome-wide association studies chemistry.chemical_compound Internal medicine Genetic variation medicine Humans Risk factor Triglycerides metabolites postprandial triglyceride response Netherlands lipoprotein metabolism Meal Triglyceride digestive oral and skin physiology Genetic Variation General Medicine Lipase Middle Aged Lipid Metabolism Postprandial Period cardiovascular diseases hepatic lipase Postprandial Endocrinology chemistry Genetic Loci Linear Models Female Hepatic lipase Lipoproteins HDL Genome-Wide Association Study |
| Zdroj: | Circulation: Genomic and Precision Medicine, 13(4), 289-297. LIPPINCOTT WILLIAMS & WILKINS Circulation. Genomic and precision medicine, 13(4), 289-297. Lippincott Williams and Wilkins Ltd. |
| ISSN: | 2574-8300 |
| Popis: | 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 NEO (Netherlands Epidemiology of Obesity) study (n=5630) 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 minutes by the residuals of a nonlinear regression that predicted TG at 150 minutes as a function of fasting TG. Association analyses were adjusted for age, sex, and principal components in a linear regression model. Next, using the identified variants as determinants, we performed linear regression analyses on the residuals of the postprandial response of 149 nuclear magnetic resonance-based metabolite measures. Results: GWAS of fasting TG and postprandial serum TG at 150 minutes 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 minutes (beta=-0.11;P-value=5.1x10(-8)). Rs7350789-A was associated with responses of 33 metabolite measures (P-value |
| Databáze: | OpenAIRE |
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