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

    685 Citationer (Scopus)

    Abstrakt

    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
    OriginalsprogEngelsk
    TidsskriftP L o S Genetics
    Vol/bind7
    Udgave nummer3
    Sider (fra-til)e1001324
    ISSN1553-7390
    DOI
    StatusUdgivet - 2011

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