Evidence from clinical and epidemiological studies indicates that asthma is associated with allergic diseases including hay fever, allergic rhinitis, and eczema. Genetic analysis demonstrated that asthma had a positive genetic correlation with allergic diseases. A Mendelian randomization (MR) analysis using the rs16969968 single-nucleotide variant as the instrumental variable indicated that smoking was associated with increased risk of asthma. However, in a different MR analysis, smoking was significantly associated with reduced hay fever and reduced allergic sensitization risk. These findings revealed inconsistencies in the association of smoking with asthma and allergic diseases. Hence, we conducted an updated MR analysis to investigate the causal association between lifetime smoking and asthma risk by using 124 genetic variants as the instrumental variables. No significant pleiotropy was detected using the MR–Egger intercept test. We found that increased lifetime smoking was significantly associated with decreased asthma risk by using the inverse variance weighted (IVW) method (OR = 0.97, 95% CI 0.956–0.986, and P = 1.77E-04), the weighted median regression method (OR = 0.976, 95% CI 0.96–0.994, and P = 8.00E-03), and the MR–Egger method (OR = 0.919, 95% CI 0.847–0.998, and P = 4.5E-02). Importantly, MR pleiotropy residual sum and outlier (MR-PRESSO) MR analysis also indicated a significant association between increased lifetime smoking and decreased asthma risk with OR = 0.971, 95% CI 0.956–0.986, and P = 2.69E-04. After the outlier was removed, MR-PRESSO outlier test further supported the significant association with OR = 0.971, 95% CI 0.959–0.984, P = 1.57E-05.

临床和流行病学研究的证据表明，哮喘与过敏性疾病有关，包括花粉症，过敏性鼻炎和湿疹。遗传分析表明，哮喘与变态反应性疾病呈正相关。使用rs16969968单核苷酸变体作为工具变量的孟德尔随机（MR）分析表明，吸烟与哮喘风险增加相关。但是，在不同的MR分析中，吸烟与花粉症减少和过敏性致敏风险降低显着相关。这些发现揭示了吸烟与哮喘和过敏性疾病之间的矛盾。因此，我们使用124种遗传变异作为工具变量，进行了更新的MR分析，以研究终生吸烟与哮喘风险之间的因果关系。使用MR–Egger截距测试未检测到明显的多效性。我们发现，使用逆方差加权（IVW）方法，终生吸烟增加与哮喘风险降低显着相关（OR = 0.97、95％CI 0.956–0.986和P = 1.77E-04），加权中位数回归方法（OR = 0.976、95％CI 0.96-0.994和 P = 8.00E-03），以及MR–Egger方法（OR = 0.919、95％CI 0.847–0.998和 P= 4.5E-02）。重要的是，MR多效性残留总和和异常值（MR-PRESSO）MR分析还表明，终生吸烟与哮喘风险降低之间存在显着相关性，OR = 0.971，95％CI 0.956-0.986P= 2.69E-04。移除异常值后，MR-PRESSO异常值测试进一步支持显着关联，OR = 0.971，95％CI 0.959–0.984，P = 1.57E-05。