Zhang Xiangyu, Zhang Runlong, Zhang Yuanfeng, Lu Tao
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China.
Front Psychiatry. 2023 Jul 5;14:1185088. doi: 10.3389/fpsyt.2023.1185088. eCollection 2023.
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 disorder (ADHD) is causally related to allergic asthma, allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis using the two-sample Mendelian Randomization (MR) approach.
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 ( = 1,415,804). The summary statistics of outcome data were obtained from the FinnGen datasets including allergic asthma (10,877 cases and 180,942 controls), allergic rhinitis (8,430 cases and 298,829 controls), pollen allergy (4555cases and 301,734 controls), allergic urticaria (1792 cases and 299,491 controls) and allergic conjunctivitis (15,567 cases and 293,587 controls). Inverse variance weighted, MR-Egger, weighted median, were used to estimate the causal association between ADHD and allergic diseases. Cochran's Q test was 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.
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; = 0.0039] lightly increased the risk of allergic asthma. 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, = 0.5457), and weighted median (OR: =1.0341, 95% CI: 0.9785-1.0929, = 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 (IVW) method, weighted median method, and MR-Egger regression.
Although several studies have found a link between ADHD and allergic diseases, our findings do not support that ADHD could increase allergic diseases incidence. Randomized controlled trials or Mendelian randomization studies with larger samples are still needed to draw more precise conclusions.
在一些观察性研究中，注意力缺陷多动障碍与过敏性疾病有关，但研究结果存在争议。本研究旨在使用两样本孟德尔随机化（MR）方法确定注意力缺陷多动障碍（ADHD）与过敏性哮喘、过敏性鼻炎、花粉过敏、过敏性荨麻疹和过敏性结膜炎是否存在因果关系。
我们进行了一项两样本孟德尔随机化（MR）研究，选择了来自精神基因组学联盟（PGC）的与注意力缺陷多动障碍（ADHD）水平高度相关的单核苷酸多态性（SNP），以20183例病例和35191例对照作为我们的工具变量。结局数据集包括全基因组关联研究（GWAS）荟萃分析（n = 1415804）。结局数据的汇总统计信息来自芬兰基因数据集，包括过敏性哮喘（10877例病例和180942例对照）、过敏性鼻炎（8430例病例和298829例对照）、花粉过敏（4555例病例和301734例对照）、过敏性荨麻疹（1792例病例和299491例对照）和过敏性结膜炎（15567例病例和293587例对照）。采用逆方差加权法、MR-Egger法、加权中位数法估计ADHD与过敏性疾病之间的因果关联。采用Cochran's Q检验量化工具变量的异质性。敏感性分析采用MR-Egger截距检验、逐一剔除分析和漏斗图。
孟德尔随机化（MR）分析表明，逆方差加权法中ADHD[比值比（OR）=1.0612；95%置信区间（CI）：1.0192 - 1.1049；P = 0.0039]轻度增加了过敏性哮喘的风险。在加权中位数的MR敏感性分析中，发现了类似的关联。但在其他方法中未发现ADHD对过敏性哮喘风险有影响的证据：MR-Egger法（OR = 0.9592，95% CI：0.8384 - 1.0974，P = 0.5457）和加权中位数法（OR = 1.0341，95% CI：0.9785 - 1.0929，P = 0.2330）。此外，使用逆方差加权（IVW）法、加权中位数法和MR-Egger回归未发现ADHD对其他过敏性疾病（过敏性鼻炎、花粉过敏、过敏性荨麻疹和过敏性结膜炎）发病率有影响的有力证据。
尽管多项研究发现ADHD与过敏性疾病之间存在联系，但我们的研究结果不支持ADHD会增加过敏性疾病发病率的观点。仍需要进行更大样本量的随机对照试验或孟德尔随机化研究以得出更精确的结论。
