Table 2.
Significant associations of genetic variation in CHI3L1 with lung function and YKL-40 protein levels.
| Cohort | SNP | Position relative to TSS | Genomic coordinates | Location | Minor Allele | MAF | HW P-value | Risk Allele | FEV1 post-BD PP P-value | Serum YKL-40 P-value |
|---|---|---|---|---|---|---|---|---|---|---|
| Discovery EA YCAAD | ||||||||||
| rs884209 | 8462 | 201413912 | 3′ UTR | A | 0.44 | 0.57 | A | 0.085 | 0.160 | |
| rs12141494 | 4326 | 201418048 | Intron 6 | A | 0.45 | 0.44 | A | 0.085 | 0.170 | |
| rs880633 | 2950 | 201419424 | Exon5 | C | 0.45 | 0.53 | C | 0.085 | 0.164 | |
| rs1538372 | 1219 | 201421155 | Intron 2 | A | 0.37 | 0.08 | G | 0.213 | 0.031 | |
| rs4950928 | -131 | 201422505 | Promoter | G | 0.22 | 0.85 | C | 0.213 | 8.1 × 10-5 | |
| rs10399931 | -329 | 201422703 | 5′ UTR | C | 0.26 | 0.52 | C | 0.136 | 1.1 × 10-4 | |
| rs10920579 | -3221 | 201425595 | 5′ UTR | A | 0.21 | 0.96 | G | 0.221 | 6.7 × 10-5 | |
| rs6698204 | -3432 | 201425806 | 5′ UTR | G | 0.44 | 0.58 | A | 0.085 | 0.039 | |
| rs4950929 | -4375 | 201426749 | 5′ UTR | G | 0.21 | 0.96 | T | 0.221 | 6.7 × 10-5 | |
| rs946263 | -9630 | 201432004 | 5′ UTR | G | 0.19 | 0.95 | A | 0.198 | 6.7 × 10-5 | |
| rs2486064 | -13013 | 201435387 | 5′ UTR | A | 0.41 | 0.38 | G | 0.660 | 0.030 | |
| Validation EA SARP | ||||||||||
| rs2364572 | 9165 | 201413209 | 3′ UTR | T | 0.04 | 0.42 | T | 0.006 | NA | |
| rs2275353 | 5678 | 201416696 | Intron 7 | A | 0.18 | 1.00 | G | 0.017 | 1 | |
| rs12141494 | 4326 | 201418048 | Intron 6 | G | 0.46 | 0.75 | A | 0.005 | 0.001 | |
| rs1538372 | 1219 | 201421155 | Intron 2 | A | 0.31 | 1 | G | 1 | 0.006 | |
| rs4950928 | -131 | 201422505 | Promoter | G | 0.20 | 0.82 | C | 1 | 0.011 | |
| rs10399805 | -247 | 201422621 | 5′ UTR | A | 0.14 | 0.65 | G | 0.035 | 1 | |
| rs946261 | -2122 | 201424496 | 5′ UTR | G | 0.38 | 0.27 | A | 0.011 | 0.053 | |
| African Ancestry | ||||||||||
| rs6691378 | -1371 | 201423745 | 5′ UTR | A | 0.27 | 0.72 | A | 1 | 0.006 |
For all the genotyped SNPs and phenotypic associations, see online supplement, Table E2.
Genomic coordinates in Chromosome 1 using the Human Genome NCBI Build 36.1 (March, 2006)
All P values are adjusted for age and gender. Followed by correction for multiple comparison. FDR threshold for the discovery-EA YCAAD cohort < 0.1. Bonferroni threshold for the Validation EA SARP and AA cohorts < 0.05
Definition of Abbreviations: SNP = Single Nucleotide Polymorphism; TSS: Transcription start site; MAF = Minor Allele Frequency; HW = Hardy-Weinberg; FEV1 = Forced Expiratory Volume in One Second; PP= Percent of predicted; Post-BD=Post-bronchodilator; YCAAD = Yale Center for Asthma and Airways Disease; SARP = Severe Asthma Research Program; UTR = Untranslated Region.