Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody

PURPOSE: Whether Vitamin D deficiency or insufficiency is associated with thyroid autoimmunity was debated for long time. This study was still to explore the causal relationship of 25 (OH) D with a thyroid peroxidase antibody (TPOAb). METHODS: The data were obtained from a cross-sectional study, SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. 10636 participants were finally included in this study. Genotyped four 25 (OH) D-related and four TPOAb-associated single nucleotide polymorphisms (SNPs) created their genetic risk scores (GRS). Bidirectional mendelian randomization (MR) analysis was used in this study. RESULTS: 25 (OH) D GRS was significantly associated with 25 (OH) D (B −0.093, 95% CI −0.111, −0.074) and TPOAb level (B 0.067, 95% CI 0.002 to 0.132). TPOAb GRS was significantly associated with TPOAb concentration (B 0.345, 95% CI 0.135 to 0.556), but not 25 (OH) D (B −0.030, 95% CI −0.091 to 0.030). Using 25 (OH) D_GRS as instrumental variable in the MR analysis, a causal relationship of genetically determined 25 (OH) D with increased TPOAb concentration (B −0.720, 95% CI −1.429 to −0.012). No relation was found between genetically instrumented TPOAb and 25 (OH) D. CONCLUSION: A higher VD_GRS was associated with higher risk of increased TPOAb concentration, which supports a causal association between decreased vitamin D and increased concentration of TPOAb in an eastern Chinese population.