Data_Sheet_1_The associations between asthma and common comorbidities: a comprehensive Mendelian randomization study.PDF

BackgroundAsthma is a chronic respiratory disease and is often associated with multiple comorbidities. The causal relationship between asthma and these comorbidities is still unclear. This study aimed to investigate the association between genetically predicted asthma and common comorbidities.
MethodsAfter searching PubMed and GWAS summary statistics, we identified 26 comorbidities of asthma. The causal relationship between asthma and comorbidities was assessed in two independent GWASs by bidirectional Mendelian randomization, followed by validation of the results using a multivariate Mendelian randomization analysis and several sensitivity analyses.
ResultsIn the bidirectional Mendelian randomization analysis, chronic sinusitis [odds ratio (OR) = 1.54, p = 1.40 × 10−5], atopic dermatitis (OR = 1.36, p = 9.37 × 10−21), allergic conjunctivitis (OR = 2.07, p = 4.32 × 10−6), and allergic rhinitis (OR = 1.53, p = 5.20 × 10−6) were significantly associated with increased asthma risk. Hyperthyroidism (OR = 1.12, p = 0.04) had a potential increased risk for asthma. For the reverse direction, asthma showed significant associations with an increased risk of chronic obstructive pulmonary disease (OR = 1.24, p = 2.25 × 10−9), chronic sinusitis (OR = 1.61, p = 5.25 × 10−21), atopic dermatitis (OR = 2.11, p = 1.24 × 10−24), allergic conjunctivitis (OR = 1.65, p = 6.66 × 10−35), allergic rhinitis (OR = 1.90, p = 2.38 × 10−57), and a potential higher risk of allergic urticaria (OR = 1.25, p = 0.003).
ConclusionThis study suggested a significant bidirectional association of chronic sinusitis, atopic dermatitis, allergic conjunctivitis, and allergic rhinitis with asthma. In addition, hyperthyroidism was associated with an increased risk of asthma and asthma increased the risk of chronic obstructive pulmonary disease and allergic urticaria.

研究背景：哮喘是一种慢性呼吸系统疾病，常伴随多种合并症。目前哮喘与这些合并症之间的因果关联仍不明确。本研究旨在探究遗传预测的哮喘与常见合并症之间的关联。
研究方法：通过检索PubMed数据库及全基因组关联研究（Genome-Wide Association Study, GWAS）汇总统计数据，本研究筛选出26种哮喘合并症。借助两项独立的全基因组关联研究，采用双向孟德尔随机化（Mendelian randomization）方法评估哮喘与各合并症间的因果关联，随后通过多变量孟德尔随机化分析及多项敏感性分析对结果进行验证。
研究结果：在双向孟德尔随机化分析中，慢性鼻窦炎[比值比（odds ratio, OR）=1.54，P=1.40×10⁻⁵]、特应性皮炎（OR=1.36，P=9.37×10⁻²¹）、过敏性结膜炎（OR=2.07，P=4.32×10⁻⁶）及过敏性鼻炎（OR=1.53，P=5.20×10⁻⁶）与哮喘风险升高显著相关；甲状腺功能亢进症（OR=1.12，P=0.04）则可能增加哮喘发病风险。反向分析显示，哮喘与慢性阻塞性肺疾病（OR=1.24，P=2.25×10⁻⁹）、慢性鼻窦炎（OR=1.61，P=5.25×10⁻²¹）、特应性皮炎（OR=2.11，P=1.24×10⁻²⁴）、过敏性结膜炎（OR=1.65，P=6.66×10⁻³⁵）、过敏性鼻炎（OR=1.90，P=2.38×10⁻⁵⁷）风险升高显著相关，且可能升高过敏性荨麻疹发病风险（OR=1.25，P=0.003）。
研究结论：本研究证实慢性鼻窦炎、特应性皮炎、过敏性结膜炎及过敏性鼻炎与哮喘之间存在显著的双向关联；此外，甲状腺功能亢进症与哮喘风险升高相关，而哮喘可增加慢性阻塞性肺疾病及过敏性荨麻疹的发病风险。