Association between hypothyroidism subtypes and major depression: A two-sample Mendelian randomization study

The causal relationship between different hypothyroidism subtypes and the risk of major depression (MD) is yet to be fully elucidated. This study aimed to determine if there's a causal relationship between various hypothyroidism subtypes (and related factors) and the risk of MD. This genetic association study utilized a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between various hypothyroidism subtypes and MD risk. Genome-Wide Association Study (GWAS) summary statistics were obtained from the FinnGen and the UK Biobank. Instrumental variables (IVs) were chosen based on single nucleotide polymorphisms (SNPs). Among the analyzed hypothyroidism subtypes and related factors, "Hypothyroidism, strict autoimmune" (HTCBSA) and "Hypothyroidism, levothyroxin purchases" (HT/LP) demonstrated a statistically significant positive causal relationship with MD, with odds ratios of 1.020 (95 % CI: 1.004–1.037) and 1.022 (95 % CI: 1.005–1.040), respectively. The sensitivity analysis supported the robustness of these findings, showing no significant horizontal pleiotropy and confirming the stability of results when individual SNPs were removed. "Congenital iodine-deficiency syndrome/hypothyroidism" (CIDS/HT), "Postinfectious hypothyroidism" (PHT), "Hypothyroidism due to medicaments and other exogenous substances" (HDTDM and OES), "Thyroid Stimulating Hormone" (TSH), "Thyrotropin-releasing hormone" (THRH), and "Hypothyroidism, strict autoimmune, 3 medication purchases required" (HTCBSA/3MPR) showed no significant causal relationship with MD. The study population was limited to individuals of European ancestry, and there may be certain genetic differences between different ethnic groups. This MR study suggests a potential causal relationship between certain hypothyroidism subtypes (specifically HTCBSA and HT/LP) and an increased risk of MD.