Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

Semin Liver Dis. 2015 Nov;35(4):375-91. doi: 10.1055/s-0035-1567870. Epub 2015 Dec 16.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / surgery
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Graft Rejection / genetics
  • Graft Survival / genetics
  • Humans
  • Insulin Resistance / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lipase / genetics
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / surgery
  • Liver Transplantation
  • Lysophospholipase / genetics
  • Membrane Proteins / genetics
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / surgery
  • Obesity / genetics
  • Obesity / metabolism
  • Polymorphism, Genetic
  • Protein Phosphatase 1 / genetics
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • GCKR protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • TM6SF2 protein, human
  • TRIB1 protein, human
  • Protein Serine-Threonine Kinases
  • Lipase
  • adiponutrin, human
  • Lysophospholipase
  • LYPLAL1 protein, human
  • PPP1R3B protein, human
  • Protein Phosphatase 1