IDDF2022-ABS-0106 Iron status and non-alcoholic fatty liver disease: a mendelian randomization study

Abstract

<h3>Background</h3> Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. Observational studies found increased iron intake and serum ferritin among NAFLD patients. But whether iron status is causally related to NAFLD is uncertain. Here we studied the association of genetically determined iron status with the risk of NAFLD using Mendelian randomization (MR). <h3>Methods</h3> This is a two-sample MR study. We applied single nucleotide polymorphisms (SNPs) for iron status proxied by serum iron, ferritin, transferrin and transferrin saturation from the Genetics of Iron Status Consortium (n=48,973), in a genome-wide association study of 1664 NAFLD cases and 400055 controls from the UK Biobank. We selected SNPs that reached genome-wide significance (p&lt;5x10^-8) in linkage equilibrium (r²≤0.01). We only kept the SNPs for the biomarker they have the strongest association with and excluded those associated with confounders. Their effects on NAFLD were calculated using inverse variance weighting. <h3>Results</h3> The risk of NAFLD is negatively associated with genetically predicted serum transferrin [odds ratio (OR)=0.80, 95% confidence interval (CI): 0.66 to 0.97] but not iron (OR=0.90, 95% CI: 0.63 to 1.29), ferritin (OR=1.33, 95% CI: 0.54 to 3.30) or transferrin saturation (OR=0.98, 95% CI: 0.65 to 1.48) (IDDF2022-ABS-0106 Table 1,Characteristics of SNPs used). <h3>Conclusions</h3> MR analysis provided evidence that genetically predicted higher serum transferrin may be protective against NAFLD.