Causal Relationship Between Genetically Determined Free Fatty Acids and Nonalcoholic Fatty Liver Disease: A Mendelian Randomization Study

遗传决定的游离脂肪酸与非酒精性脂肪肝疾病之间的因果关系:一项孟德尔随机化研究

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Abstract

OBJECTIVE: This study aimed to evaluate whether the ten-individual plasma-level of free fatty acids (FFAs) affect the risk of nonalcoholic fatty liver disease (NAFLD) which is featured by triglycerides (TGs) deposition because the observational studies are limited and conflicting about the causal effect between FFAs and NAFLD. DESIGN AND METHODS: This analysis was a large genome-wide association study (GWAS) summary statistic. Fourteen independent single-nucleotide polymorphisms (SNPs) without linkage disequilibrium (r (2) < 0.005) that were strongly associated (p < 5 × 10(-8)) with FFAs were chosen as instrumental variables to estimate the causal effect of genetic variants on the levels of 10 phospholipid FAs through GWAS, and summary estimates were obtained using the inverse-variance weighted (IVW) method applied to SNPs. And the summary-level data of European participants from the eMERGE network, the FinnGen cohorts, the UK Biobank, and the Estonian Biobank, for the latest and largest GWAS datasets for NAFLD (8434 cases and 770,180 controls), were obtained. Mendelian randomization analysis was applied. RESULTS: The result demonstrated that 10 individual FFAs were not significantly associated with NAFLD. CONCLUSION: The evidence to support the causal association of the individual plasma FFAs with NAFLD is insufficient in this study.

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