Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

Elizabeth K Speliotes, Laura M Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J Kim, Cameron D Palmer, Vilmundur Gudnason, Gudny Eiriksdottir, Melissa E Garcia, Lenore J Launer, Michael A Nalls, Jeanne M Clark, Braxton D Mitchell, Alan R Shuldiner, Johannah L Butler, Marta Tomas, Udo Hoffmann, Shih-Jen Hwang, Joseph M Massaro, Christopher J O'DonnellDushyant V Sahani, Veikko Salomaa, Eric E Schadt, Stephen M Schwartz, David S Siscovick, Benjamin F Voight, J Jeffrey Carr, Mary F Feitosa, Tamara B Harris, Caroline S Fox, Albert V Smith, W H Linda Kao, Joel N Hirschhorn, Ingrid B Borecki, NASH CRN

    779 Citations (Scopus)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p
    Original languageEnglish
    JournalP L o S Genetics
    Volume7
    Issue number3
    Pages (from-to)e1001324
    ISSN1553-7390
    DOIs
    Publication statusPublished - 2011

    Keywords

    • Adaptor Proteins, Signal Transducing
    • Adult
    • Aged
    • Aged, 80 and over
    • Blood Glucose
    • Case-Control Studies
    • Chondroitin Sulfate Proteoglycans
    • Cohort Studies
    • Fatty Liver
    • Genome-Wide Association Study
    • Humans
    • Insulin
    • Lectins, C-Type
    • Lipase
    • Male
    • Membrane Proteins
    • Middle Aged
    • Mutation, Missense
    • Nerve Tissue Proteins
    • Polymorphism, Single Nucleotide
    • Quantitative Trait Loci
    • Tomography, X-Ray Computed

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