Genetic Variations and Nonalcoholic Fatty Liver Disease: Field Synopsis, Systematic Meta-Analysis, and Epidemiological Evidence

Abstract

Objective: To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease (NAFLD).

Methods: Literature from Web of Science, PubMed, and Embase between January 1980 and September 2022 was systematically searched. Meta-analyses of the genetic variants were conducted using at least five data sources. The epidemiologic credibility of the significant associations was graded using the Venice criteria.

Results: Based on literature screening, 399 eligible studies were included, comprising 381 candidate gene association, 16 genome-wide association, and 2 whole-exome sequencing studies. We identified 465 genetic variants in 173 genes in candidate gene association studies, and 25 genetic variants in 17 genes were included in the meta-analysis. The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD, with cumulative epidemiological evidence of an association graded as strong for two variants in two genes ( HFE, TNF), moderate for four variants in three genes ( TM6SF2, GCKR, and ADIPOQ), and weak for five variants in five genes ( MBOAT7, PEMT, PNPLA3, LEPR, and MTHFR).

Conclusion: This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD, which may help understand the genetic architecture of NAFLD risk.

Keywords: Genetic association study; Genetic variant; Meta-analysis; Nonalcoholic fatty liver disease; Systematic review.