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

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 t...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	lipidomics genomics <i>FADS1</i> <i>FADS2</i> postprandial Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/534cbdc7bfb045188f2c3d5d7dd79527
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spelling	oai:doaj.org-article:534cbdc7bfb045188f2c3d5d7dd795272021-11-25T18:35:54ZGenomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study10.3390/nu131140002072-6643https://doaj.org/article/534cbdc7bfb045188f2c3d5d7dd795272021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4000https://doaj.org/toc/2072-6643Postprandial 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<sup>−8</sup>/132 = 4 × 10<sup>−10</sup>), 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/<i>FADS1</i> and <i>FADS2</i>) on chromosome 11 had <i>p</i> < 8.0 × 10<sup>−7</sup> for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with <i>p</i> < 3.3 × 10<sup>−3</sup>. CpGs around the <i>FADS1/2</i> region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (<i>p</i> = 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.Marguerite R. IrvinMay E. MontasserTobias KindSili FanDinesh K. BarupalAmit PatkiRikki M. TannerNicole D. ArmstrongKathleen A. RyanSteven A. ClaasJeffrey R. O’ConnellHemant K. TiwariDonna K. ArnettMDPI AGarticlelipidomicsgenomics<i>FADS1</i><i>FADS2</i>postprandialNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4000, p 4000 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lipidomics genomics <i>FADS1</i> <i>FADS2</i> postprandial Nutrition. Foods and food supply TX341-641
spellingShingle	lipidomics genomics <i>FADS1</i> <i>FADS2</i> postprandial Nutrition. Foods and food supply TX341-641 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 Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
description	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<sup>−8</sup>/132 = 4 × 10<sup>−10</sup>), 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/<i>FADS1</i> and <i>FADS2</i>) on chromosome 11 had <i>p</i> < 8.0 × 10<sup>−7</sup> for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with <i>p</i> < 3.3 × 10<sup>−3</sup>. CpGs around the <i>FADS1/2</i> region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (<i>p</i> = 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.
format	article
author	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
author_facet	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
author_sort	Marguerite R. Irvin
title	Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
title_short	Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
title_full	Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
title_fullStr	Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
title_full_unstemmed	Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
title_sort	genomics of postprandial lipidomics in the genetics of lipid-lowering drugs and diet network study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/534cbdc7bfb045188f2c3d5d7dd79527
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Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study

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