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Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.
Chen, Yanhua; Du, Xiaomeng; Kuppa, Annapurna; Feitosa, Mary F; Bielak, Lawrence F; O'Connell, Jeffrey R; Musani, Solomon K; Guo, Xiuqing; Kahali, Bratati; Chen, Vincent L; Smith, Albert V; Ryan, Kathleen A; Eirksdottir, Gudny; Allison, Matthew A; Bowden, Donald W; Budoff, Matthew J; Carr, John Jeffrey; Chen, Yii-Der I; Taylor, Kent D; Oliveri, Antonino; Correa, Adolfo; Crudup, Breland F; Kardia, Sharon L R; Mosley, Thomas H; Norris, Jill M; Terry, James G; Rotter, Jerome I; Wagenknecht, Lynne E; Halligan, Brian D; Young, Kendra A; Hokanson, John E; Washko, George R; Gudnason, Vilmundur; Province, Michael A; Peyser, Patricia A; Palmer, Nicholette D; Speliotes, Elizabeth K.
Afiliação
  • Chen Y; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Du X; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Kuppa A; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Feitosa MF; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Bielak LF; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • O'Connell JR; Department of Endocrinology, Diabetes and Nutrition, University of Maryland - Baltimore, Baltimore, MD, USA.
  • Musani SK; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Guo X; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Kahali B; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Chen VL; Centre for Brain Research, Indian Institute of Science, Bangalore, India.
  • Smith AV; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Ryan KA; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Eirksdottir G; Department of Endocrinology, Diabetes and Nutrition, University of Maryland - Baltimore, Baltimore, MD, USA.
  • Allison MA; Icelandic Heart Association, Kopavogur, Iceland.
  • Bowden DW; Department of Family Medicine, University of California San Diego, San Diego, CA, USA.
  • Budoff MJ; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
  • Carr JJ; Department of Internal Medicine, Lundquist Institute at Harbor-UCLA, Torrance, CA, USA.
  • Chen YI; Department of Radiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Taylor KD; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Oliveri A; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Correa A; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Crudup BF; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Kardia SLR; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Mosley TH; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Norris JM; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Terry JG; Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
  • Rotter JI; Department of Radiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Wagenknecht LE; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Halligan BD; Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
  • Young KA; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Hokanson JE; Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
  • Washko GR; Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
  • Gudnason V; Department of Medicine, Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, MA, USA.
  • Province MA; Icelandic Heart Association, Kopavogur, Iceland.
  • Peyser PA; Department of Medicine, University of Iceland, Reykjavik, Iceland.
  • Palmer ND; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Speliotes EK; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Nat Genet ; 55(10): 1640-1650, 2023 10.
Article em En | MEDLINE | ID: mdl-37709864
Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnostic code (3,584 cases versus 621,081 controls) measured NAFLD across diverse ancestries. We identified NAFLD-associated variants at torsin family 1 member B (TOR1B), fat mass and obesity associated (FTO), cordon-bleu WH2 repeat protein like 1 (COBLL1)/growth factor receptor-bound protein 14 (GRB14), insulin receptor (INSR), sterol regulatory element-binding transcription factor 1 (SREBF1) and patatin-like phospholipase domain-containing protein 2 (PNPLA2), as well as validated NAFLD-associated variants at patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), apolipoprotein E (APOE), glucokinase regulator (GCKR), tribbles homolog 1 (TRIB1), glycerol-3-phosphate acyltransferase (GPAM), mitochondrial amidoxime-reducing component 1 (MARC1), microsomal triglyceride transfer protein large subunit (MTTP), alcohol dehydrogenase 1B (ADH1B), transmembrane channel like 4 (TMC4)/membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and receptor-type tyrosine-protein phosphatase δ (PTPRD). Implicated genes highlight mitochondrial, cholesterol and de novo lipogenesis as causally contributing to NAFLD predisposition. Phenome-wide association study (PheWAS) analyses suggest at least seven subtypes of NAFLD. Individuals in the top 10% and 1% of genetic risk have a 2.5-fold to 6-fold increased risk of NAFLD, cirrhosis and hepatocellular carcinoma. These genetic variants identify subtypes of NAFLD, improve estimates of disease risk and can guide the development of targeted therapeutics.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepatopatia Gordurosa não Alcoólica Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hepatopatia Gordurosa não Alcoólica Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos