DataSheet_1_Genetic analyses of the bidirectional associations between common mental disorders and asthma.pdf

ObjectiveAlthough extensive research has explored the link between mental disorders and asthma, the characteristics and patterns of this association are still unclear. Our study aims to examine the genetic causal links between common mental disorders (specifically, anxiety and depression) and asthma.
MethodsWe conducted genetic analyses including linkage disequilibrium score regression (LDSC) and bidirectional two-sample Mendelian randomization (MR) analyses, and utilized summary statistics from recent large-scale Genome-Wide Association Studies (GWASs) in European populations, covering sensation of anxiety or depression, anxiety sensation, depression sensation, anxiety disorders, major depression disorder (MDD), and asthma.
ResultsLDSC revealed significant genetic correlations among sensation of anxiety or depression, MDD and asthma (P < 0.017), highlighting potential genetic correlation between anxiety disorders and asthma (P < 0.05 yet > 0.017). In bidirectional two-sample MR, inverse-variance weighted (IVW) analyses suggested that genetic liability to asthma was significantly associated with an increased risk of sensation of anxiety or depression (OR = 4.760, 95%CI: 1.645–13.777), and MDD (OR = 1.658, 95%CI: 1.477–1.860). Conversely, IVW analyses indicated that genetic liability to anxiety disorders was not associated with an increased risk of asthma (P > 0.01), nor was genetic liability to asthma associated with an increased risk of anxiety disorders (P > 0.01). Furthermore, no significant genetic causal relationships were observed for other studied traits. Multivariate MR, after adjusting for body mass index and alcohol consumption, further corroborated the independent causal effect of genetic predisposition to MDD on the risk of asthma (OR = 1.460, 95% CI: 1.285–1.660).
ConclusionOur study establishes MDD as a predisposing factor for asthma. Meanwhile, anxiety disorders are not causal risk factors for asthma, nor is the reverse true. It is recommended to closely monitor asthma symptoms in patients with MDD.

研究目标
尽管已有广泛研究探索了精神障碍与哮喘之间的关联，但二者关联的特征与模式仍未明确。本研究旨在探究常见精神障碍（具体为焦虑与抑郁）与哮喘之间的遗传因果关联。

研究方法
本研究开展了包括连锁不平衡得分回归（linkage disequilibrium score regression, LDSC）与双向两样本孟德尔随机化（bidirectional two-sample Mendelian randomization, MR）在内的遗传分析，并利用了欧洲人群近期大规模全基因组关联研究（Genome-Wide Association Studies, GWAS）的汇总统计数据，涵盖焦虑或抑郁感受、焦虑感受、抑郁感受、焦虑障碍、重度抑郁障碍（major depression disorder, MDD）以及哮喘。

研究结果
LDSC分析显示，焦虑或抑郁感受、MDD与哮喘之间存在显著遗传相关（P < 0.017），同时提示焦虑障碍与哮喘之间存在潜在遗传相关（P < 0.05但>0.017）。在双向两样本MR分析中，逆方差加权（inverse-variance weighted, IVW）分析表明，哮喘的遗传易感性与焦虑或抑郁感受风险升高显著相关（优势比（odds ratio, OR）=4.760，95%置信区间（confidence interval, CI）：1.645–13.777），且与MDD风险升高显著相关（OR=1.658，95%CI：1.477–1.860）。反之，IVW分析显示，焦虑障碍的遗传易感性与哮喘风险升高无显著关联（P > 0.01），哮喘的遗传易感性与焦虑障碍风险升高亦无显著关联（P > 0.01）。此外，其余研究表型未观察到显著遗传因果关系。在校正体重指数与饮酒行为后，多变量MR分析进一步证实了MDD遗传易感性对哮喘风险的独立因果效应（OR=1.460，95%CI：1.285–1.660）。

研究结论
本研究证实MDD是哮喘的易感因素。同时，焦虑障碍并非哮喘的因果风险因素，反之亦然。临床中建议对MDD患者密切监测哮喘症状。