The association between bipolar disorder and thyroid dysfunction: a bidirectional two- sample Mendelian randomization study

Abstract

Background Both bipolar disorder (BD) and thyroid dysfunction contribute significantly to the global burden on the quality of life of the population. Previous studies have observed a potential association between BD and thyroid dysfunction. Our aim was to analyze the causal relationship between BD and thyroid dysfunction.Methods We ran a group of bidirectional two-sample Mendelian randomization (MR) analyses based on summary data of genome-wide association studies (GWASs) of European individuals to estimate the causal relationship between BD (N = 413,466) and thyroid dysfunction (N = 462,933). A threshold of P < 0.05 was deemed of potential evidence for a causal effect. Instrument variables (IVs) were included based on the genome-wide significance threshold (P < 5 × 10− 8) and linkage disequilibrium (LD) clumping (r2 < 0.001). In total, 41 and 39 single nucleotide polymorphisms (SNPs) from the Psychiatric Genomics Consortium (PGC) associated with BD were employed as genetic instruments for hypothyroidism and hyperthyroidism, respectively. In the reverse MR analysis, 99 and 11 variants extracted from hypothyroidism and hyperthyroidism were utilized as genetic instruments, which were obtained from recent large-scale Genome-Wide Association Studies (GWAS). Outlier assessment and sensitivity analyses of results were performed to confirm the robustness.Results Analyses suggested that BD was negatively associated with hypothyroidism (OR 0.996; 95%CI 0.993–0.999; P = 0.003). Hyperthyroidism was negatively associated with BD(OR 1.68*10− 5;95%CI 1.72*10− 7–0.002༛P = 2.52*10− 6). However, no evidence suggested an association between hypothyroidism and the risk of BD, as well as BD and the risk of hyperthyroidism.Conclusions This study provides evidence that the presence of BD is associated with a decreased risk of hypothyroidism. Meanwhile, the presence of hyperthyroidism is associated with a decreased risk of developing BD. These findings hold significant implications for future research endeavors aimed at improving treatment approaches for individuals with BD and exploring the etiology of BD.