Genetically Predicted 25‐Hydroxyvitamin D Levels on Hypothyroidism: A Two‐Sample Mendelian Randomization

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Abstract Background Alterations in levels of 25-Hydroxyvitamin D have been associated with the risk of thyroid disease. This study uses Mendelian randomization (MR) to infer the possible causal association of 25-Hydroxyvitamin D with hypothyroidism. Methods We performed two-sample MR using the summary statistics data from genome-wide association studies (GWAS) from populations with European ancestry to infer the causality of genetically controlled levels of 25-Hydroxyvitamin D on the risk of hypothyroidism, Hashimoto’s thyroiditis, as well as biochemical parameters of thyroid diseases. The inverse-variance method (IVW) was used as the primary method to calculate the combined effect of all SNPs. Other methods were adopted to evaluate the stability and reliability of the results. Comprehensive sensitivity analyses were conducted to ensure that none of the MR analysis’s primary assumptions were violated. Results The results of the IVW analysis revealed a significant causal association between higher levels of 25-Hydroxyvitamin D and lower risk of hypothyroidism (beta = −0.197, 95% CI (− 0.301, −0.093); SE = 0.053, P beta = 2.256×10 -4 ) as well as increased levels of free T4 (beta = 0.204, 95% CI (0.305, 0.094); SE = 0.056, P beta = 3.0506×10 −4 ). On the other hand, no significant causality was determined for higher levels of 25-Hydroxyvitamin D in association with Hashimoto’s thyroiditis (beta=-0.047, 95% CI (−0.245, 0.151), p=0.641) and TSH levels (beta = −0.024, 95% CI (−0.099, - 0.051); P beta = 0.524). Conclusion The results of this two-sample MR study provide evidence supporting the potential of 25-Hydroxyvitamin D supplementation in reducing the risk of hypothyroidism.

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