{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen Y"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NIDA NIH HHS","NIA NIH HHS","NHLBI NIH HHS","NIMHD NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health"],"pagination":["1640-1650"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10918428"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["55(10)"],"pubmed_abstract":["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."],"journal":["Nature genetics"],"pubmed_title":["Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease."],"pmcid":["PMC10918428"],"funding_grant_id":["U01 HL084756","UL1 TR001881","N01 HC095166","N01 HC095165","N01 HC095168","N01 HC095167","R01 HL060944","HHSN268201800014C","N01 HC095169","R01 DK131787","R01 DK106621","N01 HC095160","P30 DK072488","U01 HL089897","N01 HC095162","N01 HC095161","N01 HC095164","U01 HL089856","HHSN268201800014I","N01 HC095163","R01 HL085571","HHSN268201800010I","HHSN268201500001C","UL1 TR000040","R01 HL060919","N02 HL064278","N01AG12100","R01 HL087700","R01 HL061019","R01 DK089256","R01 HL117078","HHSN268201800013I","R01 HL087660","P30 DK063491","HHSN268201500001I","R01 HL061210","RC1 HL100245","UL1 TR001420","R01 DK085175","R01 DK128871","N01 HC025195","R01 HL060894","75N92020D00007","HHSN268201800012C","U01 HL072515","HHSN268201800012I","75N92019D00031","75N92020D00001","75N92020D00002","R01 HL122464","R01 DK118062","75N92020D00005","75N92020D00006","R01 HL071739","75N92020D00003","75N92020D00004","HHSN268201500003C","UL1 TR001079","R01 DK106621, RO1 DK107904","N01 HC095159","U01 HL137181","HHSN271201200022C","HHSN268201800015I","HHSN268201800011C","HHSN268201800011I","R01 HL105756","R01 DK107904","HHSN268201500003I"],"pubmed_authors":["Kuppa A","Halligan BD","Bowden DW","Kardia SLR","Rotter JI","Province MA","Guo X","Washko GR","Feitosa MF","Du X","Correa A","Gudnason V","Bielak LF","Hokanson JE","Speliotes EK","Budoff MJ","Wagenknecht LE","Chen VL","Mosley TH","Allison MA","Chen Y","Smith AV","O'Connell JR","Ryan KA","Carr JJ","Taylor KD","Musani SK","Terry JG","Palmer ND","Eirksdottir G","Kahali B","Oliveri A","Chen YI","Peyser PA","Crudup BF","Young KA","Norris JM"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.","description":"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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2026-05-29T10:04:36.624Z","creation":"2025-04-07T02:08:02.918Z"},"accession":"S-EPMC10918428","cross_references":{"pubmed":["37709864"],"doi":["10.1038/s41588-023-01497-6"]}}