Vitamin D and Nonalcoholic Fatty Liver Disease: Bi-directional Mendelian Randomization Analysis

Background: Vitamin D deficiency is associated with nonalcoholic fatty liver disease (NAFLD) in many cross-sectional studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and NAFLD.

Methods: 9182 participants were included from a survey in East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS) for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related single nucleotide polymorphisms. Presence of liver steatosis was assessed using ultrasound. Instrumental variable was used to measure the causal relationship between them.

Results: An SD increase in the 25(OH)D GRS was significantly associated with 25(OH)D (β 1.29, 95%CI -1.54, -1.04, P<0.05) but not with NAFLD (OR 0.97, 95%CI 0.92, 1.01). An SD increase in NAFLD GRS was also strongly associated with NAFLD (OR 1.09, 95%CI 1.04, 1.15, P<0.05) but not with 25(OH)D (β -0.15, 95%CI -0.41, 0.10). Using an instrumental variable estimator, no associations were found for genetically instrumented 25(OH)D with NAFLD and for genetically instrumented NAFLD with 25(OH)D.

Conclusion: Our results support the conclusion that there is no causal association between vitamin D and NAFLD using a bi-directional MR approach in a Chinese population.