Causal association between chloride intracellular channel protein 5 and Hashimoto thyroiditis: A Mendelian...

This objective was to conduct Mendelian randomization (MR) analysis in order to investigate the potential causal relationship between chloride intracellular channel protein 5 (CLIC5) and Hashimoto thyroiditis (HT). Two separate MR analyses were performed, both using CLIC5 as the exposure variable and HT as the outcome. The first analysis utilized exposure data from genome-wide association study (GWAS) ID: prot-a-584 and outcome data from GWAS ID: ebi-a-GCST90018635. The second analysis used the same exposure data but sourced the outcome from ebi-a-GCST90018855. Four MR methods were applied in both analyses: MR Egger, weighted median, inverse variance weighted, and weighted mode. In both analyses, the inverse variance weighted method produced the most significant results, indicating a positive association between CLIC5 and HT. The first analysis estimated a causal effect of 0.4169 (P = .005344), while the second analysis estimated a slightly lower effect of 0.1196 (P = .0009933). The weighted median and weighted mode also suggested a positive association, although with lower statistical significance. The MR Egger method did not provide evidence for a causal effect in either analysis. Heterogeneity statistics did not indicate any significant evidence of heterogeneity, and the causal direction test strongly supported the hypothesis that CLIC5 caused HT. Horizontal pleiotropy was not detected. The consistency of the findings across different outcome databases enhances the credibility of the observed causal effect between CLIC5 and HT. Although the effect estimates varied slightly, these variations can be attributed to differences in the underlying genetic architectures captured by the respective GWAS studies.