Potential causal associations between vitamin D and uric acid: Bidirectional mediation analysis

Vitamin D deficiency, a major public-health worldwide, is associated with hyperuricemia but casual association is questioned. The study was conducted to determine potential causal associations between 25-hydroxy vitamin D (25(OH) D) and uric acid (UA). A cross-sectional study of the Electricity Generating Authority of Thailand (EGAT(3)) cohort was conducted. Subjects (n = 2,288) were used to genotype the group-specific component (GC) at rs2282679 and ATP-binding cassette subfamily G member 2 (ABCG2) at rs2231142. Mediation analysis with 1000-replication bootstrap was applied to construct causal pathways i.e., rs2282679 -> 25(OH) D -> UA and rs2231142 -> UA -> 25(OH) D: The mediator (i.e., 25(OH) D and UA) was firstly regressed on the studied gene (i.e., rs2282679 and rs2231142). A potential causal effect of C allele on UA through 25(OH) D was -0.0236 (95% CI: -0.0411, -0.0058), indicating every minor C allele resulted in decreasing the 25(OH) D and then significantly decreased the UA by 0.0236 unit. For the second pathway, the mediation effect was 0.0806 (95% CI: 0.0107, 0.1628); every T allele copy for rs2231142 increased UA and thus increased 25(OH) D by 0.0806 unit. Our study suggested potential causal associations between the GC gene and UA through the 25(OH) D mediator, and the ABCG2 and the 25(OH) D through the UA mediator but the absolute effects are very clinically small.