title: Potential causal associations between vitamin D and uric acid: Bidirectional mediation analysis.
abstract: 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 (EGAT3) 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.
authors.affiliation: Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.affiliation: Department of Family Medicine, Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Thunyarat
authors.initials: T
authors.lastname: Anothaisintawee
authors.affiliation: Division of Endocrinology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
authors.forename: Laor
authors.initials: L
authors.lastname: Chailurkit
authors.affiliation: Medical and Health Office, Electricity Generating Authority of Thailand, Nonthaburi, Thailand.
authors.forename: Wipa
authors.initials: W
authors.lastname: Ratanachaiwong
authors.affiliation: Division of Cardiology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
authors.forename: Sukit
authors.initials: S
authors.lastname: Yamwong
authors.affiliation: Division of Cardiology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
authors.forename: Piyamitr
authors.initials: P
authors.lastname: Sritara
authors.affiliation: Division of Endocrinology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
authors.forename: Boonsong
authors.initials: B
authors.lastname: Ongphiphadhanakul