Fig. 1

Study overview. Primary ASMCs from 75 donors were isolated in Chicago and then cultured in Chicago (genotyping, methylation, and expression studies) and Boston (contractile response measurements to methacholine) using identical protocols. In the final 24 h in both locations, cells were exposed to either vehicle, IL-13, IL-17A, or IL-13+IL17A. Genome-wide methylation and expression data were used to conduct differential response studies as well as to map molecular QTLs (eQTLs and meQTLs). Contractile response data were used as quantitative traits to investigate the differential response to cytokine exposure followed by methacholine exposure and to map cellular QTLs (coQTLs). The numbers of samples available for each assay after QC (with genotype data also available) are shown in parentheses. Independently, lung function studies were carried out in a human population. A quantitative measure of responsiveness to methacholine was assessed in these subjects (bronchial responsiveness index (BRI)), and a GWAS was performed. The resulting BRI GWAS SNPs, along with the molecular QTLs and cellular QTLs, were enriched among asthma GWAS SNPs