Table 1.
Single variants significantly associated with the lower SaKnorm tertile in adjusted SKAT-O analysis
| Variants Associated with the Lower SaKnorm Tertile | ||||
|---|---|---|---|---|
| Chromosome | 1 | 19 | 1 | 1 |
| hg19 position | 225565015 | 55673145 | 225569241 | 225533931 |
| Allele | T>C | C>T | T>G | A>G |
| Gene | DNAH14 | DNAAF3 | DNAH14 | DNAH14 |
| P valueall | 1.11E-05* | 1.14E-05* | 1.66E-05* | 6.13E-05 |
| P valueCFTRhomozygotes | 9.50E-08* | 7.06E-07* | 1.72E-07* | 8.48E-05 |
| Odds ratio (allele) | 1.43 (T) | 2.85 (T) | 1.42 (T) | 1.42 (G) |
| rsID | rs3856154 | rs58824375 | rs950210 | rs17522489 |
| AAFcases | 0.43 | 0.07 | 0.43 | 0.21 |
| AAFcontrols | 0.33 | 0.03 | 0.33 | 0.15 |
| Change | p.Leu4096Pro | p.Gly245Ser | p.Phe4244Cys | p.Gln3556Arg |
| GERP | 4.32 | 2.52 | 1.16 | 5.45 |
| CADD (phred) | 8.00 | 8.90 | 8.54 | 7.09 |
| PolyPhen-2 | Benign | Benign | Benign | Benign |
| SIFT | Tolerated | Tolerated | Deleterious | Tolerated |
Definition of abbreviations: AAF = alternate allele frequency; CADD = combined annotation–dependent depletion; CFTR = cystic fibrosis transmembrane conductance regulator; GERP = Genomic Evolutionary Rate Profiling; PolyPhen-2 = Polymorphism Phenotyping software tool; rsID = single-nucleotide polymorphism identifier; SaKnorm = lung function based on forced expiratory volume in 1 second adjusted for age, height, and sex, then mortality among individuals affected by cystic fibrosis; SIFT = Sorting Tolerant from Intolerant algorithm.
Test results are presented when all cases within the lower SaKnorm tertile were included (P valueall) and when cases were restricted to CFTR p.Phe508del homozygotes (P valueCFTRhomozygotes). GERP scores (21) greater than 3 suggest that a variant occurs at a conserved sequence position; CADD (22) phred–scaled scores greater than 15 suggest that a variant is likely to be deleterious; and both PolyPhen-2 (23) and SIFT (24) scores predict variant deleteriousness.
Significant after strict Bonferroni correction.