Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study

Marguerite R. Irvin; May E. Montasser; Tobias Kind; Sili Fan; Dinesh K. Barupal; Amit Patki; Rikki M. Tanner; Nicole D. Armstrong; Kathleen A. Ryan; Steven A. Claas; Jeffrey R. O’Connell; Hemant K. Tiwari; Donna K. Arnett

doi:10.3390/nu13114000

Nutrients (Nov 2021)

Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study

Marguerite R. Irvin,
May E. Montasser,
Tobias Kind,
Sili Fan,
Dinesh K. Barupal,
Amit Patki,
Rikki M. Tanner,
Nicole D. Armstrong,
Kathleen A. Ryan,
Steven A. Claas,
Jeffrey R. O’Connell,
Hemant K. Tiwari,
Donna K. Arnett

Affiliations

Marguerite R. Irvin: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
May E. Montasser: Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Tobias Kind: NIH West Coast Metabolomics Center, UC Davis Genome Center, University of California, Davis, CA 95616, USA
Sili Fan: NIH West Coast Metabolomics Center, UC Davis Genome Center, University of California, Davis, CA 95616, USA
Dinesh K. Barupal: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Amit Patki: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Rikki M. Tanner: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Nicole D. Armstrong: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Kathleen A. Ryan: Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Steven A. Claas: College of Public Health, University of Kentucky, Lexington, KY 40536, USA
Jeffrey R. O’Connell: Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Hemant K. Tiwari: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Donna K. Arnett: College of Public Health, University of Kentucky, Lexington, KY 40536, USA

DOI: https://doi.org/10.3390/nu13114000
Journal volume & issue: Vol. 13, no. 11
p. 4000

Abstract

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Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10−8/132 = 4 × 10−10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p −7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p −3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.

Published in Nutrients

ISSN: 2072-6643 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Home economics: Nutrition. Foods and food supply
Website: https://www.mdpi.com/journal/nutrients

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