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
Hauptverfasser: Krawczyk, Marcin, Liebe, Roman, Lammert, Frank
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container_start_page 1865
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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source MEDLINE; Elsevier ScienceDirect Journals Complete; Alma/SFX Local Collection
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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