AUTHOR=Du Xiaomi , DeForest Natalie , Majithia Amit R. 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.777075

DOI=10.3389/fendo.2021.777075

ISSN=1664-2392

ABSTRACT=Non-alcoholic fatty liver disease (NAFLD) encompasses a continuous progression of pathophysiologic stages with varying degrees of reversibility. In addition to the inherent heterogeneity arising from defining discrete stages in a continuous disease process, diagnostic standardization is challenged by a wide variety of diagnostic technologies and proposed criteria including scores derived from liver biopsies, non-invasive imaging, serum biomarkers and varying combinations of these. Nevertheless, NAFLD is heritable, and genetic association studies have successfully identified loci, some of which have shown therapeutic promise. This mini-review provides an overview of the heterogeneity in NAFLD phenotypes and diagnostic methods, discusses genetic variants in relation to the specific stages for which they were identified, and offers a perspective on how the field can advance to better identify targets for drug discovery.