Causal effects of Hirschsprung's disease on psychiatric disorders in the European population: a two-sample Mendelian randomization study

Background: Previous studies have suggested a potential association between Hirschsprung's disease (HSCR) and psychiatric disorders. However, the causal relationship between HSCR and psychiatric disorders remains unclear. Therefore, we use Mendelian randomization to explore the causal relationship between HSCR and depression, anxiety, attention deficit and hyperactivity disorder(ADHD), and autism spectrum disorder(ASD). Methods: Genome-wide association Studies (GWAS) meta-analyses with the largest possible sample size and independent individuals from European ancestry were selected. The genetic data for depression and anxiety are from FinnGen consortium, while the genetic data for ADHD and ASD are from the Psychiatric Genomics Consortium. Inverse variance weighted (IVW) was the main analysis method. The heterogeneity of the instrumental variables (IVs) was assessed using IVW and MR-Egger, and the horizontal pleiotropy of the IVs was assessed using MR-Egger and MR-PRESSO. Results: The IVW analysis revealed a significant causal relationship between HSCR and ADHD(OR=1.010，95%CI=1.002-1.018；P=0.0119). However, there is no evidence to suggest a causal relationship between HSCR and depression, anxiety, and ASD. Furthermore, our sensitivity analysis did not reveal any evidence of heterogeneity or horizontal pleiotropy. Conclusion: Our results suggest that HSCR increases the risk of ADHD. Therefore, greater attention should be paid to the psychological health of children with HSCR.