Abstract
Attention-deficit/hyperactivity disorder (ADHD) and autoimmune diseases have been found to be correlated in the observational studies, but the causal relationships have not been fully investigated. Two-sample Mendelian randomization (MR) analysis was used to explore the causal relationships between ADHD and 8 autoimmune disorders (systemic lupus erythematosus, Crohn disease, ulcerative colitis, type 1 diabetes, rheumatoid arthritis, psoriasis, ankylosing spondylitis [AS], and multiple sclerosis) with the publicly available genome-wide association study data in the European populations. Inverse-variance weighted (IVW), weighted median, and MR-Egger were used to estimate the causal effects. Extensive sensitivity analyses were employed to validate the 3 assumptions of MR and robustness of the results. Multivariable MR (MVMR) analysis was used to evaluate the direct causal effects adjusting for the potential confounding factors. The potential mediators of the causal effects were explored through the 2-step MR mediation analysis. With the Bonferroni corrected threshold, the IVW results indicated that genetically determined higher risk of ADHD was significantly associated with increased risk of psoriasis (IVW OR: 1.29; 95% CI: 1.11-1.49, P = 6.3e-04), but not with other autoimmune disorders. The reverse MR didn't find significant causal effects of autoimmune diseases on ADHD. MVMR analysis indicated that the significant causal effects of ADHD on psoriasis remained significant after accounting for obesity, alcohol drinking, depression, and biological sex, but became nonsignificant when adjusting for smoking. Further mediation analysis suggested smoking might partially mediate the causal effects of ADHD on psoriasis (mediated percentage: 11.16%, 95% CI: 1.54% to 20.77%, P = .023). There is a significant causal relationship between ADHD and psoriasis, but not with other autoimmune disorders. The causal effects might be mediate by smoking. Our findings suggested that early prevention and lifestyle changes (such as smoking cessation) might be helpful to reduce the risk of developing psoriasis for ADHD patients. Further investigations were warranted to explore the underlying mechanisms and the potential clinical applications.