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

## TL;DR

This study used genetic data to investigate if free fatty acids cause nonalcoholic fatty liver disease but found no significant causal link.

## Contribution

The study provides a Mendelian randomization analysis to clarify the causal relationship between free fatty acids and NAFLD.

## Key findings

- Ten individual free fatty acids were not significantly associated with nonalcoholic fatty liver disease.
- Genetic evidence does not support a causal link between plasma free fatty acids and NAFLD.

## Abstract

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.

This analysis was a large genome-wide association study (GWAS) summary statistic. Fourteen independent single-nucleotide polymorphisms (SNPs) without linkage disequilibrium (r2 < 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.

The result demonstrated that 10 individual FFAs were not significantly associated with NAFLD.

The evidence to support the causal association of the individual plasma FFAs with NAFLD is insufficient in this study.