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

To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease (NAFLD). 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. 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). 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. [ABSTRACT FROM AUTHOR]