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 ).