Causal effects of pediatric asthma on psychiatric disorders: a bidirectional Mendelian randomization study

Previous studies have suggested a potential link between pediatric asthma and psychiatric disorders. However, the causal relationship between pediatric asthma and psychiatric disorders is unclear. Therefore, we used Mendelian randomization to explore causal relationships between pediatric asthma and depression, anxiety disorders, and attention deficit and hyperactivity disorder (ADHD). 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 is 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 the horizontal pleiotropy of the IVs was assessed using MR-Egger. The IVW results showed a significant causal relationship between pediatric asthma and depression (OR = 1.08, 95% CI = 1.02–1.15; <i>p</i> = 0.013). However, there is no evidence to suggest a causal relationship between pediatric asthma, anxiety, and ADHD. Reverse MR suggests a significant causal relationship (OR = 1.27, 95% CI [1.14–1.41], <i>p</i> = 9.64E − 06) between ADHD and pediatric asthma using the IVW method. Our findings suggest a causal relationship between pediatric asthma and an increased risk of depression. Additionally, we found that ADHD is significantly associated with a higher risk of pediatric asthma.

既往研究已提示儿童哮喘与精神障碍间存在潜在关联，但二者间的因果关系仍未明确。为此，本研究采用孟德尔随机化（Mendelian randomization）方法，探究儿童哮喘与抑郁症、焦虑症及注意缺陷多动障碍（ADHD）之间的因果关联。本研究纳入了针对欧洲血统独立个体、样本量最大的全基因组关联研究（GWAS）荟萃分析数据集。抑郁症与焦虑症的遗传数据取自FinnGen联盟，而注意缺陷多动障碍的遗传数据则来自精神疾病基因组学联盟（Psychiatric Genomics Consortium）。逆方差加权（IVW）为本次研究的主要分析方法。研究通过IVW法评估工具变量（IVs）的异质性，并借助MR-Egger检验工具变量的水平多效性。IVW分析结果显示，儿童哮喘与抑郁症间存在显著因果关联（比值比OR=1.08，95%置信区间CI=1.02~1.15；*p*=0.013）。但未发现儿童哮喘与焦虑症、ADHD间存在因果关联的相关证据。反向MR分析结果表明，采用IVW法时，ADHD与儿童哮喘间存在显著因果关联（OR=1.27，95%CI=[1.14~1.41]，*p*=9.64×10^-6）。本研究结果证实，儿童哮喘与抑郁症发病风险升高存在因果关联；此外还发现，ADHD与儿童哮喘的发病风险升高显著相关。