■先前的观察性研究显示,补充维生素治疗甲状腺疾病的结果相互矛盾。维生素与甲状腺疾病之间的因果关系尚不清楚。因此,我们进行了一项双样本双向孟德尔随机化(MR)研究,以探讨循环维生素水平与甲状腺疾病的相关性.
■我们使用全基因组关联研究(GWAS)数据进行了双向MR分析。循环维生素水平的遗传工具变量包括维生素A,B9,B12,C,D,E,甲状腺疾病的遗传工具变量包括自身免疫性甲状腺功能亢进,自身免疫性甲状腺功能减退症,甲状腺结节(TNs),甲状腺癌(TC)。逆方差加权乘法随机效应(IVW-RE)主要用于MR分析,使用加权中位数(WM)和MREgger作为辅助方法评估循环维生素水平与甲状腺疾病之间的关系.敏感性和多能性通过Cochran'sQ检验进行评估,MR-PRESSO,径向MR,MR-Egger回归和留一法分析。
■MR阳性证据表明循环维生素C水平是自身免疫性甲状腺功能减退症的保护因素(ORIVW-RE=0.69,95CI:0.58-0.83,p=1.05E-04)。反向MR证据表明,自身免疫性甲状腺功能亢进的遗传易感性与循环维生素A水平降低有关(ORIVW-RE=0.97,95%CI:0.95-1.00,p=4.38E-02),TNs的遗传易感性与循环维生素D水平升高相关(ORIVW-RE=1.02,95%CI:1.00-1.03,p=6.86E-03).在其他循环维生素水平与甲状腺疾病之间未检测到因果关系和反向因果关系。
我们的研究结果提供了遗传证据,支持循环维生素水平与甲状腺疾病之间的双向因果关系。这些发现为临床应用维生素防治甲状腺疾病提供了信息。
UNASSIGNED: Previous observational studies have shown conflicting results of vitamins supplementation for thyroid diseases. The causal relationships between vitamins and thyroid diseases are unclear. Therefore, we conducted a two-sample bidirectional Mendelian randomization (MR) study to explore association of circulating vitamin levels with thyroid diseases.
UNASSIGNED: We performed a bidirectional MR analysis using genome-wide association study (GWAS) data. Genetic tool variables for circulating vitamin levels include vitamins A, B9, B12, C, D, and E, Genetic tool variables of thyroid diseases include autoimmune hyperthyroidism, autoimmune hypothyroidism, thyroid nodules (TNs), and Thyroid cancer (TC). Inverse-variance weighted multiplicative random effects (IVW-RE) was mainly used for MR Analysis, weighted median (WM) and MR Egger were used as supplementary methods to evaluate the relationships between circulating vitamin levels and thyroid diseases. Sensitivity and pluripotency were evaluated by Cochran\'s Q test, MR-PRESSO, Radial MR, MR-Egger regression and leave-one-out analysis.
UNASSIGNED: Positive MR evidence suggested that circulating vitamin C level is a protective factor in autoimmune hypothyroidism (ORIVW-RE=0.69, 95%CI: 0.58-0.83, p = 1.05E-04). Reverse MR Evidence showed that genetic susceptibility to autoimmune hyperthyroidism is associated with reduced level of circulating vitamin A(ORIVW-RE = 0.97, 95% CI: 0.95-1.00, p = 4.38E-02), genetic susceptibility of TNs was associated with an increased level of circulating vitamin D (ORIVW-RE = 1.02, 95% CI: 1.00-1.03, p = 6.86E-03). No causal and reverse causal relationship was detected between other circulating vitamin levels and thyroid diseases.
UNASSIGNED: Our findings provide genetic evidence supporting a bi-directional causal relationship between circulating vitamin levels and thyroid diseases. These findings provide information for the clinical application of vitamins prevention and treatment of thyroid diseases.