Investigating Causal Relationships between Inflammatory Bowel Disease and Autism Spectrum Disorder: A Bidirectional Two-sample Mendelian Randomization Study

Background and aims Inflammatory bowel disease (IBD) is usually comorbid with psychological disorders. Emerging observational studies have indicated the association between autism spectrum disorder (ASD) and IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), whereas the causality remains unknown. Our study aimed to explore the causal association between IBD and ASD using bidirectional two-sample Mendelian randomization (MR) design. Methods Summary: -level data from large-scale genome-wide association (GWAS) studies of IBD (International Inflammatory Bowel Disease Genetics Consortium, N cases =25,042, N controls =34,915) and ASD (Integrative Psychiatric Research-Psychiatric Genomics Consortium, N cases =18,382, N controls =27,969) were retrieved. Gene variants for IBD and ASD were selected as instrumental variables. MR analyses were performed mainly including the inverse-variance-weighted method with a series of sensitivity tests. Results Genetic predisposition to IBD was associated with a high risk of ASD (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01-1.06, P = 0.01; OR [95% CI]: 1.03 [1.01-1.05], P = 0.02 for CD; OR [95% CI]: 1.03 [1.01-1.07], P = 0.04 for UC). In contrast, no causal association was found for the genetic liability to ASD on IBD. Conclusions Our findings reveal that genetically predicted IBD is causally related to ASD, whereas the causal association of ASD on IBD is not supported. Our study highlights the early screening and surveillance of psychological symptoms, as well as sustaining support for patients with IBD. Further investigations on age-specific groups are warranted.