Causal Relationship Between Autism Spectrum Disorder and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study

ABSTRACT Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two‐sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome‐wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia ( N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR‐pleiotropy residual sum and outlier (MR‐PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001–1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004–1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999–1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes ( p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.