09 January 2018
Vitamin D, Nonalcoholic fatty liver disease, Mendelian randomization analysis, Epidemiology, 25(OH)D, 25-hydroxyvitamin D, BMI, body mass index, CI, confidence interval, GRS, genetic risk scores, HbA1c, glycated hemoglobin A1c, HDL, high-density lipoprotein, IV, instrumental variables, LDL, low-density lipoprotein, MR, mendelian randomization, NAFLD, nonalcoholic fatty liver disease, OR, odds ratio, SNP, single nucleotide polymorphism
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.
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.
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.