The causal relationship between major depression disorder and thyroid diseases: A Mendelian randomization study and mediation analysis
Xu Zhang, Lu Qiao, Yiping Luo, Luyao Wang, Yuan Tian, Xuemei Luo
Abstract
Studies have been conducted on the relationship between depression and thyroid diseases and function, its causal relationship remains unclear. Using summary statistics of genome-wide association studies of European and East Asian ancestry, we conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid function (European: normal range TSH, T4, T3, fT4, TPOAb levels and TPOAb-positives; East Asian: T4) and thyroid diseases (hypothyroidism, hyperthyroidism, and Hashimoto's thyroiditis), and used Mediation analysis to evaluate potential mediators (alcohol intake, antidepressant) of the association and calculate the mediated proportions. It was observed a significant causal association between MDD on hypothyroidism (P = 8.94 × 10−5), hyperthyroidism (P = 8.68 × 10−3), and hashimoto's thyroiditis (P = 3.97 × 10−5) among European ancestry, which was mediated by Alcohol intake (alcohol intake versus 10 years previously for hypothyroidism (P = 0.026), hashimoto's thyroiditis (P = 0.042), and alcohol intake frequency for hypothyroidism (P = 0.015)) and antidepressant (for hypothyroidism (P = 0.008), hashimoto's thyroiditis (P = 0.010)), but not among East Asian ancestry (PMDD-hypothyroidism = 0.016, but β direction was different; PMDD-hyperthyroidism = 0.438; PMDD-hashimoto’s thyroiditis = 0.496). There was no evidence for bidirectional causal association between thyroid function mentioned above and MDD among both ancestry (all P > 0.05). We importantly observed a significant causal association between MDD on risk of hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, and Alcohol intake and antidepressant as mediators for prevention of hypothyroidism, hashimoto's thyroiditis attributable to MDD.