Identifying Shared Risk Genes between Nonalcoholic Fatty Liver Disease and Metabolic Traits by Cross-Trait Association Analysis

Abstract

Nonalcoholic fatty liver disease (NAFLD) generally co-occurs with metabolic disorders, but it is unclear which genes have a pleiotripic effect on NAFLD and metabolic traits. We performed a large-scale cross-trait association analysis to identify the overlapping genes between NAFLD and nine metabolic traits. Among all the metabolic traits, we found that obesity and type II diabetes are associated with NAFLD. Then, a multitrait association analysis among NAFLD, obesity and type II diabetes was conducted to improve the overall statistical power. We identified 792 significant variants by a cross-trait meta-analysis involving 100 pleiotripic genes. Moreover, we detected another two common genes by a genome-wide gene test. The results from the pathway enrichment analysis show that the 102 shared risk genes are enriched in cancer, diabetes, insulin secretion, and other related pathways. This study can help us understand the molecular mechanisms underlying comorbid NAFLD and metabolic disorders.