Causal Relationship between Attention-Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Two-Sample Mendelian Randomization.

Abstract

Aims/Background Despite the exponential increase in the incidence rate of Autism spectrum disorder (ASD), effective therapies for the disorder are still limited. According to vast clinical observations, the pathogeneses of ASD and Attention-deficit hyperactivity disorder (ADHD) share a great deal of similarities. This serves as a prompt to investigate, in this study, whether patients with ADHD are at a higher risk for ASD, which is significant for disease prevention. Methods Data concerning ADHD as the exposure variable and ASD as the outcome variable were collected from the publicly available Integrative Epidemiology Unit Open GWAS project (IEU GWAS) database. After screening the instrumental variables (IVs), statistical analysis was performed using the TwoSampleMR package of version R4.3.1, and sensitivity testing was conducted to evaluate the stability and reliability of the results. Results After screening the Single nucleotide polymorphisms (SNPs) through the calculation of F-value and Mendelian randomization (MR) Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), seven SNPs that satisfied the three major assumptions of Mendelian randomization were selected as IVs and could be used in place of ADHD in exploring the aforementioned causal relationship. The Odds ratio (OR) for the random-effect Inverse-variance weighted (IVW) method was 1.31 (95% Confidence interval [CI]: 1.14-1.52; p = 0.0001). A similar trend was observed for the Weighted median estimator (WME) method, with an OR of 1.37 (wider 95% CI: 1.15-1.64; p = 0.0005). Conclusion This study includes the pooled data on ADHD and ASD from the IEU GWAS public database, and there is sufficient evidence that patients with ADHD have a higher risk of ASD.