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dc.contributor.authorIrvin, Marguerite R.
dc.contributor.authorMontasser, May E.
dc.contributor.authorKind, Tobias
dc.contributor.authorFan, Sili
dc.contributor.authorBarupal, Dinesh K.
dc.contributor.authorPatki, Amit
dc.contributor.authorTanner, Rikki M.
dc.contributor.authorArmstrong, Nicole D.
dc.contributor.authorRyan, Kathleen A.
dc.contributor.authorClaas, Steven A.
dc.contributor.authorO’connell, Jeffrey R.
dc.contributor.authorTiwari, Hemant K.
dc.contributor.authorArnett, Donna K.
dc.date.accessioned2021-11-16T12:29:56Z
dc.date.available2021-11-16T12:29:56Z
dc.date.issued2021-11-01
dc.identifier.urihttp://hdl.handle.net/10713/17118
dc.description.abstractPostprandial 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 identi-fied. 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 < 8.0 × 10−7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10−3 . 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. © 2021 by the authors.en_US
dc.description.sponsorshipNational Heart, Lung, and Blood Instituteen_US
dc.description.urihttps://doi.org/10.3390/nu13114000en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofNutrientsen_US
dc.subjectFADS1en_US
dc.subjectFADS2en_US
dc.subjectGenomicsen_US
dc.subjectLipidomicsen_US
dc.subjectPostprandialen_US
dc.titleGenomics of postprandial lipidomics in the genetics of lipid-lowering drugs and diet network studyen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/nu13114000
dc.source.volume13
dc.source.issue11


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