Serum 25-hydroxyvitamin D levels and the risk of non-alcoholic fatty liver: A two-sample Mendelian randomization study
Qi Sheng1, Huanchen Shi2, Shousheng Liu3, Likun Zhuang3, Zhenzhen Zhao3, Yongning Xin4
1 Department of Infectious Disease, Qingdao Municipal Hospital, Cheeloo College of Medicine, Shandong University, Jinan; Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, Shangdong, China
2 School of Basic Medicine, College of Medicine, Qingdao University, Qingdao, Shangdong, China
3 Clinical Research Center, Qingdao, China
4 Department of Infectious Disease, Qingdao Municipal Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong; Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao 266011, Shandong Province
Source of Support: None, Conflict of Interest: None
Background: Accumulated studies have shown that low expression of 25-hydroxyvitamin D [25(OH)D] was significantly associated with the risk of non-alcoholic fatty liver disease (NAFLD). However, the exact causality is still unknown. The aim of this study was to investigate whether levels of 25(OH)D are associated with risk of NAFLD, using a two-sample Mendelian randomization (MR).
Methods: Data from a recent large vitamin D genome-wide association study (GWAS) on 417,580 Europeans were utilized, and the largest published histology-based NAFLD GWAS study (1,483 cases and 17,781 healthy controls) for genetic variants predicted to cause NAFLD were searched. All genetic datasets for the MR analyses were obtained using publicly available summary statistics based on individuals of European ancestry from the MR-Base and NHGRI-EBI GWAS Catalog database. Inverse-variance weighted (IVW) MR approach was used to estimate causal effects in the main analysis, complemented by 4 additional methods to control for pleiotropy. Sensitivity analyses were conducted to verify whether heterogeneity and pleiotropy can bias the MR results.
Results: The MR analysis did not provide strong evidence for the causal association of circulating 25(OH)D with NAFLD by IVW method (OR = 0.746, 95%CI 0.517–1.078; P = 0.119). The results were consistent using four other MR methods. Sensitivity analysis using all different analytical approaches yielded similar results. There was no evidence for pleiotropy (MR-Egger intercept: −0.0003758, P = 0.970). The replication process also showed consistent results using IVW method (P = 0.710).
Conclusion: This study indicates that serum 25(OH)D levels did not possess an obvious effect on the risk of NAFLD. The associations in previous studies may be due to residual confounding or reverse causation.