Causal relationship between antihypertensive drugs and Hashimoto’s thyroiditis: a drug-target Mendelian randomization study

Introduction and objectives Recent studies have indicated a potential association of hypertension with Hashimoto’s thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood. Methods We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations. Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications. We focused on drugs linked to a lower risk of coronary artery disease for our main analysis. We gathered genetic data on SBP and HT risk from comprehensive genome-wide association studies available for European and Asian groups. For a supplementary analysis, we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies. Results Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10 -5 ) and Asian populations (OR [95% CI]: 0.28 [0.12, 0.66]; p = 3.54×10 -3 ). Moreover, genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91, 0.97]; p = 3.57×10 -5 ) and thiazide diuretics (0.98 [0.96, 0.99]; p = 3.83×10 -3 ) showed a significant association with a decreased risk of HT only in European population. These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications. Conclusion The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT.