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    Genomics of postprandial lipidomics in the genetics of lipid-lowering drugs and diet network study

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

    Date
    2021-11-01
    Journal
    Nutrients
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/nu13114000
    Abstract
    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 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.
    Sponsors
    National Heart, Lung, and Blood Institute
    Keyword
    FADS1
    FADS2
    Genomics
    Lipidomics
    Postprandial
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17118
    ae974a485f413a2113503eed53cd6c53
    10.3390/nu13114000
    Scopus Count
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