Differences in odds ratios between severe cases versus controls and between all cases (moderate-to-severe) versus controls were assessed by permutation. Region-based conditional analyses were performed using logistic regression, adjusting for the most significant (lead) single nucleotide polymorphism (SNP) in each region using genotyped or dosage data as appropriate, and testing all SNPs within a 250kb window on either side of the lead SNP for association with affection status. To estimate the combined effect of genetic risk variants, we constructed a genetic score based on the cumulative number of risk alleles in a logistic regression in the COPDGene non-Hispanic whites including age, pack-years, and ancestry-based principal components.
