Evaluation of causal relationships between genetic liability to inflammatory bowel disease and autism spectrum disorder by Mendelian randomization analysis.

Background: 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.

Methods: Summary-level data from large-scale genome-wide association (GWAS) studies of IBD and ASD were retrieved. Mendelian randomisation analyses were performed with a series of sensitivity tests.

Results: Genetic predisposition to ASD was not associated with the risk of IBD (odds ratio [OR] = 0.99, 95% confidence interval [CI = 0.91-1.06, p = 0.70; OR [95% CI]: 1.03 [0.93-1.13], p = 0.58 for CD; OR [95% CI]: 0.96 [0.87-1.05], p = 0.37 for UC) in the IIBDGC dataset. In the FinnGen dataset, their causal effects were unfounded (OR [95% CI]: 1.04 [0.94-1.15], p = 0.49 for IBD; OR [95% CI]: 1.08 [0.89-1.31], p = 0.42 for CD; OR [95% CI]: 1.00 [0.88-1.13], p = 0.95 for UC). In the meta-analysis of two datasets, the OR was 1.01 (95% CI 0.96-1.07, p = 0.45). For the risk of ASD under genetic liability to IBD, the OR from meta-analysis was 1.03 (95% CI 1.01-1.05, p = 0.01).

Conclusion: Our findings indicate genetic predisposition to ASD might not increase the risk of IBD, whereas genetic liability to IBD is associated with an increased risk of ASD. Further investigations using more powerful datasets are warranted.