Genetic risk score (GRS) analysis and classification
In order to compute the polygenic effects of multiple SNVs, genetic risk
scores (GRS) were calculated using summary statistics from the largest
GWAS of childhood asthma published to date.(15) Our GRS used the pruning
and thresholding approach as previously described (32): 1) Identified
shared SNVs between the discovery (published GWAS summary statistics)
and target (CHILD study) cohorts; 2) Eliminated redundant signals by
pruning SNVs in high linkage disequilibrium (LD) using a window size of
50kb, shift distance of 2, and LD threshold (R2) of
> 0.8; 3) Employed a stepwise, forward regression analysis
to calculate GRS for each individual, starting with the most significant
SNV from the published GWAS, by summing the risk alleles weighted by the
effect size (β) obtained from the discovery cohort; 4) Identified a set
of genetic variants that best predicted the target trait using
regression analysis while accounting for sex and the first three PCs as
covariates.
Subjects were classified into high (1), moderate (0) and low (-1) GRS
groups: defined as high if their GRS was 1 standard deviation higher
from the mean (z score > 1), and low if 1 standard
deviation lower than the mean (z score < -1). Individuals who
fall between high and low risk group ( -1 < z score
< 1) were defined as having a moderate risk.