Causal effect of nonalcoholic fatty liver disease on Alzheimer's disease: A Mendelian randomization study

Abstract Background The current discourse revolves around the role of nonalcoholic fatty liver disease (NAFLD) as either an active participant or a passive observer in the development of Alzheimer’s disease (AD). This study seeks to evaluate the causal effects of NAFLD on Alzheimer’s disease. Methods We performed two-sample Mendelian randomization (MR) analyses to assess the causal effects of genetically predicted NAFLD (chronically elevated serum alanine aminotransferase levels [cALT]) on AD, cognition-related trait (intelligence, cognitive performance, fluid intelligence [FI] score), and education-related traits (educational attainment, education qualifications, and age completed full-time education) in the main analysis. We repeated the MR analysis using SNPs from biopsy-confirmed NAFLD and imaging-based NAFLD in the validation analysis. Results In the main analysis, the random-effect inverse variance weighted (IVW) MR analyses indicated that cALT was not statistically associated with AD (Odds ratio [OR] = 1.000, confidence interval [95%CI]: 0.988–1.011, P = 0.970), intelligence (OR = 0.995, 95%CI: 0.979–1.011, P = 0.564), cognitive performance (OR = 0.988, 95%CI: 0.972–1.004, P = 0.141), FI score (OR = 0.981, 95%CI: 0.938–1.027, P = 0.410), education qualifications (OR = 0.992, 95%CI: 0.971–1.014, P = 0.484), and age completed full-time education (OR = 1.004, 95%CI: 0.971–1.038, P = 0.827). The cALT was statistically associated with educational attainment (OR = 1.025, 95%CI: 1.002–1.049, P = 0.039). However, validation analyses reported no significant causal effects of biopsy-confirmed NAFLD and imaging-based NAFLD on any outcomes. Conclusions In conclusion, using multiple analytic approaches we did not observe the causal effects of NAFLD on AD, cognition, and education in the current two-sample MR study.