Human Genetics to Identify Therapeutic Targets for NAFLD: Challenges and Opportunities

Front Endocrinol (Lausanne). 2021 Dec 7:12:777075. doi: 10.3389/fendo.2021.777075. eCollection 2021.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a continuous progression of pathophysiologic stages that is challenging to diagnose due to its inherent heterogeneity and poor standardization across a wide variety of diagnostic measures. NAFLD is heritable, and several loci have been robustly associated with various stages of disease. In the past few years, larger genetic association studies using new methodology have identified novel genes associated with NAFLD, some of which have shown therapeutic promise. This mini-review provides an overview of the heterogeneity in NAFLD phenotypes and diagnostic methods, discusses genetic associations in relation to the specific stages for which they were identified, and offers a perspective on the design of future genetic mapping studies to accelerate therapeutic target identification.

Keywords: GWAS; NAFLD; NASH; exomes; gene discovery; human genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biomarkers / metabolism
  • Case-Control Studies
  • Diagnostic Techniques, Endocrine / trends
  • Disease Progression
  • Genetic Predisposition to Disease
  • Genetics, Population*
  • Genome-Wide Association Study
  • Human Genetics / methods
  • Human Genetics / trends
  • Humans
  • Molecular Targeted Therapy / methods*
  • Molecular Targeted Therapy / trends
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / therapy*
  • Polymorphism, Single Nucleotide

Substances

  • Biomarkers