Toward Genetic Prediction of Nonalcoholic Fatty Liver Disease Trajectories: PNPLA3 and Beyond
Nonalcoholic fatty liver disease (NAFLD) is on the verge of becoming the leading cause of liver disease. NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk...
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Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2020-05, Vol.158 (7), p.1865-1880.e1 |
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container_title | Gastroenterology (New York, N.Y. 1943) |
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creator | Krawczyk, Marcin Liebe, Roman Lammert, Frank |
description | Nonalcoholic fatty liver disease (NAFLD) is on the verge of becoming the leading cause of liver disease. NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk variants (eg, PNPLA3, TM6SF2, and SERPINA1) and key pathways involved in fatty liver disease pathobiology. Functional studies improved our understanding of these genetic factors and the molecular mechanisms underlying the trajectories from fat accumulation to fibrosis, cirrhosis, and cancer over time. Here, we summarize key NAFLD risk genes and illustrate their interactions in a 3-dimensional “risk space.” Although NAFLD genomics sometimes appears to be “lost in translation,” we envision clinical utility in trial design, outcome prediction, and NAFLD surveillance. |
doi_str_mv | 10.1053/j.gastro.2020.01.053 |
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NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk variants (eg, PNPLA3, TM6SF2, and SERPINA1) and key pathways involved in fatty liver disease pathobiology. Functional studies improved our understanding of these genetic factors and the molecular mechanisms underlying the trajectories from fat accumulation to fibrosis, cirrhosis, and cancer over time. Here, we summarize key NAFLD risk genes and illustrate their interactions in a 3-dimensional “risk space.” Although NAFLD genomics sometimes appears to be “lost in translation,” we envision clinical utility in trial design, outcome prediction, and NAFLD surveillance.</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/j.gastro.2020.01.053</identifier><identifier>PMID: 32068025</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adiponutrin ; Animals ; Genetic Predisposition to Disease ; Genetic Risk Score ; Genetic Variation ; Genome-Wide Association Study ; Genomics ; Humans ; Lipase - genetics ; Membrane Proteins - genetics ; Non-alcoholic Fatty Liver Disease - diagnosis ; Non-alcoholic Fatty Liver Disease - genetics ; Nonalcoholic Steatohepatitis ; Phenotype ; Risk Assessment ; Risk Factor ; Risk Factors ; Risk Prediction</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 2020-05, Vol.158 (7), p.1865-1880.e1</ispartof><rights>2020 AGA Institute</rights><rights>Copyright © 2020 AGA Institute. 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subjects | Adiponutrin Animals Genetic Predisposition to Disease Genetic Risk Score Genetic Variation Genome-Wide Association Study Genomics Humans Lipase - genetics Membrane Proteins - genetics Non-alcoholic Fatty Liver Disease - diagnosis Non-alcoholic Fatty Liver Disease - genetics Nonalcoholic Steatohepatitis Phenotype Risk Assessment Risk Factor Risk Factors Risk Prediction |
title | Toward Genetic Prediction of Nonalcoholic Fatty Liver Disease Trajectories: PNPLA3 and Beyond |
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