Zhang Shuo, Wang Ting, Zeng Ping
Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Jiangsu Engineering Research Center of Biological Data Mining and Healthcare Transformation, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Prev Sci. 2025 Apr;26(3):343-354. doi: 10.1007/s11121-025-01793-z. Epub 2025 Mar 5.
Maternal smoking during pregnancy exhibited an adverse influence on asthma, but its joint effect with genetic factors remained elusive. Moreover, whether there existed a moderating role of genetic susceptibility in this effect on childhood/adolescent-onset asthma (COA) and adult-out asthma (AOA) was unknown. We employed the UK Biobank cohort to estimate the effect of maternal smoking during pregnancy on the risk of offspring asthma (41,828 AOA and 15,120 COA). We investigated genetic influence on asthma and assessed the moderating role of genetic susceptibility in this effect by incorporating polygenetic risk score (PRS) and performing a stratified analysis in distinct genetic risk populations. Hazard ratio (HR) and 95% confidence intervals (CIs) were reported. We found that participants whose mother smoked during pregnancy were more likely to occur asthma (HR = 1.14, 95%CIs 1.12 ~ 1.16), with similar effects for AOA and COA. Additionally, we observed a significant association between genetic factors and asthma (HR = 1.70, 95%CIs 1.66 ~ 1.74), with a higher genetic influence on COA (HR = 2.16, 95%CIs 2.09 ~ 2.23) compared to AOA (HR = 1.84, 95%CIs 1.76 ~ 1.93). Furthermore, we revealed that genetic factors could modify the effect of maternal smoking during pregnancy on asthma especially among childhood and adolescents, with participants having high genetic risk versus low genetic risk (HR = 1.13 vs. 1.02, P = 0.035). We provided supportive evidence that maternal smoking during pregnancy and the genetic factors increased the risk of offspring asthma in whole population. We further revealed that genetic susceptibility exerted more pronounced influence on COA compared to AOA, and played a moderating role in this effect.
孕期母亲吸烟对哮喘有不良影响，但其与遗传因素的联合作用仍不清楚。此外，遗传易感性在这种对儿童/青少年期起病哮喘（COA）和成人起病哮喘（AOA）的影响中是否存在调节作用尚不清楚。我们利用英国生物银行队列来估计孕期母亲吸烟对后代哮喘风险的影响（41828例AOA和15120例COA）。我们研究了遗传因素对哮喘的影响，并通过纳入多基因风险评分（PRS）并在不同遗传风险人群中进行分层分析，评估了遗传易感性在这种影响中的调节作用。报告了风险比（HR）和95%置信区间（CIs）。我们发现，母亲在孕期吸烟的参与者更易患哮喘（HR = 1.14，95%CI 1.12～1.16），AOA和COA的影响相似。此外，我们观察到遗传因素与哮喘之间存在显著关联（HR = 1.70，95%CI 1.66～1.74），与AOA（HR = 1.84，95%CI 1.76～1.93）相比，遗传因素对COA的影响更大（HR = 2.16，95%CI 2.09～2.23）。此外，我们发现遗传因素可以改变孕期母亲吸烟对哮喘的影响，尤其是在儿童和青少年中，遗传风险高的参与者与遗传风险低的参与者相比（HR = 1.13对1.02，P = 0.035）。我们提供了支持性证据，表明孕期母亲吸烟和遗传因素会增加整个人群后代患哮喘的风险。我们进一步发现，与AOA相比，遗传易感性对COA的影响更为显著，并在这种影响中起调节作用。
