With the full CGS sample, we further tested the hypothesis that multiple proteins present on the apical plasma membrane contribute to lung disease severity as measured by SakNorm; the hypothesis was considered previously for meconium ileus susceptibility in CF.5 In total, 3,814 GWAS SNPs (MAF > 0.02) were annotated to within ±10 kb of 155 apical genes obtained from the Gene Ontology project.5 The JLS-Fisher test was first applied to each SNP, and the SNP-specific test statistic was then aggregated across all SNPs to perform the multivariate apical gene-set analysis. We then used an independent French sample (n = 1,232) for replication. Imputation based on 1000 Genomes26,27 (as outlined in the Online Methods of Sun et al.5) was used to assess regional association within the SLC9A3R1, SLC9A3R2, and EZR binding sites of SLC9A3.