Figure 2.

Burden testing of common and rare variants associating with lung function (SaKnorm). All variants within each 5 kb window, moving across the entire region in increments of 1,250 bp, were tested for a combined association with lung function (SaKnorm) via SKAT-O test. The x axis denotes chr7 hg19 bp position, y axis is −log10 of the regional P-value. Association values were plotted at the center of each 5 kb window. Top (red): rare variants with minor allele frequency (MAF)<1% only. Middle (blue): common variants with MAF>1% only. Bottom (purple): combined test of common and rare variants with variants weighted inversely proportional to their frequency. Vertical shaded boxes: regions of significant association in the combined analysis (α=0.01). Genome browser style tracks: Top: packed view of known CFTR regions of interest and TAD as previously reported (see Supplementary File). Middle: view of genes with exonic/intronic structure. Bottom: CCCTC-binding factor (CTFC) binding signals in two cell types, and mammalian conservation as assayed by genomic evolutionary rate profiling (GERP) (horizontal bar indicating GERP score of 4). CFTR, the protein defective in cystic fibrosis; TAD, topologically associated domain.