Table 4.
Multivariate model results with top 15 SNPs (ranked by p-value) associated with time to CGD, stratified by transplant center.(n=979) All variant data from dbSNP Build 132
| SNP | Genec | Variant | HRa | 95% CI | P Value | Minor allele in AA | MAF in AA | Minor allele in non-AA | MAF in non-AA |
|---|---|---|---|---|---|---|---|---|---|
| rs7886938 | FMO6d | Coding-synonb | 1.60 | 1.26–2.04 | 1.47E-04 | A | 0.19 | A | 0.16 |
| rs7889839 | FMO6d | Missenseb | 1.60 | 1.25–2.04 | 1.58E-04 | G | 0.19 | G | 0.16 |
| rs2272797 | FMO6d | Missenseb | 1.57 | 1.23–2.01 | 3.15E-04 | A | 0.17 | A | 0.16 |
| rs909530 | FMO3d | Coding-synon | 1.50 | 1.20–1.87 | 3.52E-04 | T | 0.48 | T | 0.25 |
| rs3769148 | ZAK | Missense | 0.68 | 0.54–0.85 | 5.61E-04 | A | 0.11 | A | 0.47 |
| rs2369679 | AK7 | Missense | 1.58 | 1.20–2.08 | 1.07E-03 | C | 0.03 | C | 0.17 |
| rs2239360 | FANCA | Intron | 1.42 | 1.15–1.76 | 1.22E-03 | C | 0.35 | T | 0.34 |
| rs10916 | CYP1B1 | Untranslated-3 | 1.45 | 1.16–1.83 | 1.38E-03 | G | 0.3 | G | 0.21 |
| rs2242480 | CYP3A4 | Intron | 1.59 | 1.19–2.13 | 1.59E-03 | C | 0.29 | T | 0.11 |
| rs916864 | PON3 | Intronb | 0.62 | 0.46–0.84 | 1.78E-03 | T | 0.09 | T | 0.22 |
| rs609636 | CYP4F12 | Missense | 0.37 | 0.20–0.69 | 1.85E-03 | T | 0.07 | T | 0.06 |
| rs609290 | CYP4F12 | Missense | 0.37 | 0.20–0.69 | 1.89E-03 | T | 0.07 | T | 0.06 |
| rs1639 | PON2 | Intron | 0.63 | 0.47–0.85 | 2.13E-03 | G | 0.1 | G | 0.23 |
| rs7190823 | FANCA | Missense | 1.39 | 1.12–1.72 | 2.59E-03 | T | 0.32 | C | 0.42 |
| rs12448860 | FANCA | Intron | 1.37 | 1.11–1.69 | 3.17E-03 | T | 0.37 | A | 0.42 |
(Abbreviations: AA= African Americans, MAF= Minor Allele Frequency, synon=synonymous, untranslated-3= variant in the untranslated 3′ end of gene, HR= Hazard Ratio)
Analysis conducted using a Cox proportional hazards model stratified by transplant center and adjusted by recipient race. Hazard ratio and 95% CI of CGD for each risk allele. Model also adjusted for confounders such as donor age and recipient characteristics such as African-American race, smoking status, recipient-donor CMV status, and age.
UCSC predicted variant relative to gene track
There was linkage disequilibrium (LD) between the three SNPs in FMO6 namely rs7886938 and rs7886938 and rs7889839 with r2=1.0 in both non-AAs and greater than 0.88 in AA’s. The FMO3 SNP, namely rs909530 is not in LD with FMO6 SNPs in non-AAs and AAs, with r2 less than 0.8.
SNPs in FANCA, rs7190823 and rs12448860 are in LD in non-AA only with r2=0.98.
SNPs in PON2 and PON3 rs1639 and rs916864, respectively are in LD with r2= 0.84 in non-AAs and 0.90 in AAs.
SNPs in CYP4F12, rs609636 and rs609290 are in LD in r2= 1.0 in AA and non-AA.
SNPs statistically significant after accounting for an false-discovery rate of 20%.