Associations of Maternal Smoking During Pregnancy and Genetic Susceptibility with Incident Asthma from a Cohort Study

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.