Environmental exposures modulate polygenic risk of recurrent wheeze
Several environmental exposures were tested for interaction with GRS in a multiple regression model (see list in Supplemental Data 5 ) accounting for sex and the top three PCs. Breastfeeding status at 12 months of age showed a significant interaction (p=0.02) with GRS to modify prevalence of recurrent wheeze. As shown in Figure 3c , breastfeeding at 12 months was associated with a 2.2- and 1.5-fold lower prevalence of recurrent wheeze among those with low and moderate GRS, respectively. Interestingly, the prevalence of recurrent wheeze was not modified by breastfeeding among those in the high GRS group. In addition, nitrogen dioxide (NO2) exposure in the first six months of life significantly interacts with GRS to increase prevalence of recurrent wheeze for the first quarter or 0-3 months of age (p=0.005) and for the second quarter or months 4-6 (p=0.01;Supplemental Data 4 ). Figures 3d & 3edemonstrate that the prevalence of recurrent wheeze increases with genetic risk, however, the prevalence is highest for those exposed to high levels of NO2. Specifically, among those with high GRS, the prevalence was 2.7-fold higher among those exposed to high NO2 compared with low exposure from birth to 3 months of age. This effect of NO2 exposure is reduced but still significant in the second quarter (4-6 months) among those with high GRS, showing that those with high NO2 exposure had a 1.5-fold higher prevalence of wheeze compared to those with low exposure.
Interaction analysis did not identify any modifying effects of environmental exposures on GRS for physician diagnosed asthma (Supplemental Data 6 ).