Figure 1  Apical Gene-Set Association Analysis of CF Lung Disease Severity as Measured by SaKnorm in the Canadian Gene Modifier Study Discovery Sample of 1,409 Subjects
SaKnorm24 (sex-, age-, and mortality-adjusted, normalized forced expiratory volume in 1 s; FEV1) was used as the lung function measure. In total, 3,814 GWAS SNPs (MAF > 0.02) were annotated to within ±10 kb of the 155 apical genes obtained from the Gene Ontology database.5
(A, C, E) Quantile-quantile plots (QQ-plots) of the SNP-specific association test statistics of the apical SNPs via (A) the proposed joint location-scale test (JLS-Fisher), (C) the regression based location-only test, and (E) Levene’s scale-only test. QQ-plots of the observed association statistics are shown in red, and the QQ-plots of the statistics calculated from the 10,000 phenotype-permutated replicates are shown in gray.
(B, D, F) Corresponding gene-set association analysis results for (B) the JLS-Fisher test (permutation p = 0.0099), (D) the standard regression-based location-only test (permutation p = 0.0876), and (F) Levene’s scale-only test (permutation p = 0.0222). For each figure, the observed sum statistic aggregated across all 3,814 SNPs, as described in the Material and Methods, is shown as a vertical line in red, and the sum statistics calculated from the 10,000 phenotype-permutated replicates is shown as a histogram.