Cell Reports Medicine (Nov 2021)
Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
- Nooshin Ghodsian,
- Erik Abner,
- Connor A. Emdin,
- Émilie Gobeil,
- Nele Taba,
- Mary E. Haas,
- Nicolas Perrot,
- Hasanga D. Manikpurage,
- Éloi Gagnon,
- Jérôme Bourgault,
- Alexis St-Amand,
- Christian Couture,
- Patricia L. Mitchell,
- Yohan Bossé,
- Patrick Mathieu,
- Marie-Claude Vohl,
- André Tchernof,
- Sébastien Thériault,
- Amit V. Khera,
- Tõnu Esko,
- Benoit J. Arsenault
Affiliations
- Nooshin Ghodsian
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Erik Abner
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Riia 23b, 51010, Estonia
- Connor A. Emdin
- Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
- Émilie Gobeil
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Nele Taba
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Riia 23b, 51010, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Riia 23, 51010, Estonia
- Mary E. Haas
- Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Molecular Biology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Nicolas Perrot
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Hasanga D. Manikpurage
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Éloi Gagnon
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Jérôme Bourgault
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Alexis St-Amand
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Christian Couture
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Patricia L. Mitchell
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada
- Yohan Bossé
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada
- Patrick Mathieu
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada
- Marie-Claude Vohl
- Centre NUTRISS, Institut sur la Nutrition et les Aliments Fonctionnels, Université Laval, Québec, QC, Canada; School of Nutrition, Université Laval, Québec, QC, Canada
- André Tchernof
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada; School of Nutrition, Université Laval, Québec, QC, Canada
- Sébastien Thériault
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, QC, Canada
- Amit V. Khera
- Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Tõnu Esko
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Riia 23b, 51010, Estonia
- Benoit J. Arsenault
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada; Corresponding author
- Journal volume & issue
-
Vol. 2,
no. 11
p. 100437
Abstract
Summary: Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-documented NAFLD in participants of European ancestry (8,434 cases and 770,180 controls). We identify 5 potential susceptibility loci for NAFLD (located at or near GCKR, TR1B1, MAU2/TM6SF2, APOE, and PNPLA3). We also report a potentially causal effect of lower LPL expression in adipose tissue on NAFLD susceptibility and an effect of the FTO genotype on NAFLD. Positive genetic correlations between NAFLD and cardiometabolic diseases and risk factors such as body fat accumulation/distribution, lipoprotein-lipid levels, insulin resistance, and coronary artery disease and negative genetic correlations with parental lifespan, socio-economic status, and acetoacetate levels are observed. This large GWAS meta-analysis reveals insights into the genetic architecture of NAFLD.
