Associations between attention-deficit/hyperactivity disorder and allergic diseases: A two-sample Mendelian randomization study

Abstract

Abstract Background In some observational studies, attention-deficit/hyperactivity disorder has been linked to allergic diseases, but the findings are debatable. This study aimed to determine whether attention-deficit/hyperactivity are causally related to allergic asthma, allergic rhinitis, pollen allergy, allergic urticaria and allergic conjunctivitis using the two-sample Mendelian Randomization (MR) approach. Methods We did a two-sample Mendelian randomization (MR) study, which chose single nucleotide polymorphisms (SNPs) that are highly associated with attention-deficit/hyperactivity disorder (ADHD) levels from the Psychiatric Genomics Consortium (PGC) on 20,183 cases and 35,191 controls as our instruments. Outcomes datasets included genome-wide association study (GWAS) meta-analysis (n = 1415804). The summary statistics of outcome data were obtained from the FinnGen datasets including allergic asthma (10877 cases and 180942 controls), allergic rhinitis (8430 cases and 298829 controls), pollen allergy (4555cases and 301734 controls), allergic urticaria (1792 cases and 299491 controls) and allergic conjunctivitis (15567 cases and 293587 controls). Inverse variance weighted, MR-Egger, weighted median, were used to estimate the causal association between ADHD and allergic diseases. Cochran's Q test were used to quantify the heterogeneity of instrumental variables. MR-Egger intercept test, leave-one-out analysis, and the funnel plot were all used in sensitivity analyses. Results The Mendelian randomization (MR) analysis indicated that ADHD in inverse variance weighted [odds ratio (OR) = 1.0612; 95% confidence interval (CI):1.0192–1.1049; p = 0.0039] increased the risk of allergic asthma lightly. In MR sensitivity analyses of the weighted median, a similar association was found. But no evidence for an effect of ADHD on allergic asthma risk was found in additional methods: MR-Egger (OR = 0.9592, 95% CI: 0.8384–1.0974, p = 0.5457), and weighted median (OR: =1.0341, 95% CI: 0.9785–1.0929, p = 0.2330). Also, no strong evidence for an effect of ADHD on other allergic diseases (allergic rhinitis, pollen allergy, allergic urticaria and allergic conjunctivitis) incidence was found using the inverse-variance weighted method, weighted median method and MR-Egger regression. Conclusions Although several studies have found a link between ADHD and allergic diseases, our findings do not support that ADHD could increase allergic diseases incidence. Randomised controlled trials or Mendelian randomization studies with larger samples are still needed to draw more precise conclusions.