Causal association between body mass index and autoimmune thyroiditis: evidence from Mendelian randomization.

ABSTRACT

BACKGROUND: Recent studies have reported associations between body mass index (BMI) and various autoimmune disorders. However, it is still uncertain whether there exists a direct cause-and-effect relationship between BMI and autoimmune thyroiditis (AIT). The aim of our study is to investigate the causal association between BMI and AIT. METHODS: We conducted a two-sample summary data Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary statistics data related to BMI as exposure, and GWAS summary statistic data sets for AIT as the outcome. Robustly associated single-nucleotide polymorphisms (SNPs) for BMI were selected as instrumental variables (IVs). We used the inverse variance weighted (IVW) method as the primary method and performed other MR methods such as MR-Egger regression, weighted median, simple mode, and weighted mode analyses for further validation. The slope of MR-Egger regression was used to correct for pleiotropy and provide estimates of causality. The p-value for the intercept in MR-Egger was utilized to detect any directional pleiotropic effects. Heterogeneity and sensitivity analyses were performed to assess the robustness of our findings. RESULTS: Seventy-eight SNPs were selected from GWAS on BMI as the IVs. Our MR analysis using the IVW method showed a potential causal association between BMI and AIT (OR = 3.071, 95% CI 1.324-7.118). Findings from other MR methods are non-significant, although the direction of effect is consistent. There was no evidence that the result was affected by genetic pleiotropy (MR-Egger regression intercept = 0.01, SE = 0.00025, p = 0.719). Heterogeneity and sensitivity analyses revealed no significant heterogeneity among SNPs, and no single SNP drove the observed associations. CONCLUSION: Our findings suggest a potential causal association between BMI and AIT, which may provide a basis for further investigation into the relationship between BMI and AIT. Further studies are required as only the IVW method shows significant results, and the case sample size is small.