Independent significant SNP associations with GVHD death and infection deaths
| . | . | . | . | Cohort 1 . | Cohort 2 . | Meta analyses of cohorts 1 and 2 . | |||
|---|---|---|---|---|---|---|---|---|---|
| Primary cause of death/SNP . | SNP position on chr 2 (hg19) . | Allele (ref/risk) . | Risk allele frequency (C1/C2) . | HR (95% CI) . | P . | HR (95% CI) . | P . | HR (95% CI) . | P . |
| GVHD | |||||||||
| rs2241131* | 102804041 | A/C | 0.69/0.72 | 1.46 (1.05-2.02) | .024 | 2.71 (1.53-4.82) | 6.7 × 10−4 | 1.69 (1.28-2.25) | 2.6 × 10−4 |
| rs2310241* | 102841949 | C/A | 0.51/0.54 | 1.37 (1.01-1.84) | .04 | 1.81 (1.25-2.62) | 1.6 × 10−3 | 1.53 (1.21-1.92) | 3.3 × 10−4 |
| Infection | |||||||||
| rs11676124* | 102941338 | T/C | 0.62/0.61 | 1.7 (1.2-2.4) | 3 × 10−3 | 2.39 (1.15-4.99) | .02 | 1.81 (1.32-2.47) | 2.2 × 10−4 |
| rs11692304 | 103095404 | G/A | 0.47/0.48 | 1.61 (1.19-2.16) | 2 × 10−3 | 1.95 (1.03-3.7) | .041 | 1.66 (1.27-2.18) | 2.2 × 10−4 |
| rs13015714 | 102971865 | G/T | 0.77/0.76 | 1.79 (1.17-2.73) | 8 × 10−3 | 2.92 (1.22-6.97) | .016 | 1.96 (1.34-2.88) | 5.3 × 10−4 |
| rs72627435* | 102897739 | T/C | 0.21/0.20 | 1.76 (1.29-2.4) | 3.8 × 10−4 | 2.01 (1.09-3.69) | .024 | 1.81 (1.37-2.38) | 2.8 × 10−5 |
| rs4851005 | 103011552 | C/T | 0.37/0.34 | 1.85 (1.38-2.47) | 3.3 × 10−5 | 2.17 (1.15-4.09) | .017 | 1.9 (1.46-2.47) | 1.9 × 10−6 |
| rs13019803 | 102776202 | C/T | 0.08/0.08 | 2.31 (1.51-3.53) | 1.1 × 10−4 | 2.53 (1.11-5.77) | .028 | 2.35 (1.61-3.43) | 8.9 × 10−6 |
| rs4851601* | 103116261 | G/A | 0.28/0.26 | 2.01 (1.48-2.73) | 8.3 × 10−6 | 1.92 (1.03-3.6) | .042 | 1.99 (1.51-2.62) | 9.7 × 10−7 |
| Multiallele | — | GCG/TTA | 1.94 (1.54-2.44) | 1.8 × 10−8 | 2.24 (1.36-3.69) | .002 | 1.99 (1.61-2.45) | 1.2 × 10−10 | |
| . | . | . | . | Cohort 1 . | Cohort 2 . | Meta analyses of cohorts 1 and 2 . | |||
|---|---|---|---|---|---|---|---|---|---|
| Primary cause of death/SNP . | SNP position on chr 2 (hg19) . | Allele (ref/risk) . | Risk allele frequency (C1/C2) . | HR (95% CI) . | P . | HR (95% CI) . | P . | HR (95% CI) . | P . |
| GVHD | |||||||||
| rs2241131* | 102804041 | A/C | 0.69/0.72 | 1.46 (1.05-2.02) | .024 | 2.71 (1.53-4.82) | 6.7 × 10−4 | 1.69 (1.28-2.25) | 2.6 × 10−4 |
| rs2310241* | 102841949 | C/A | 0.51/0.54 | 1.37 (1.01-1.84) | .04 | 1.81 (1.25-2.62) | 1.6 × 10−3 | 1.53 (1.21-1.92) | 3.3 × 10−4 |
| Infection | |||||||||
| rs11676124* | 102941338 | T/C | 0.62/0.61 | 1.7 (1.2-2.4) | 3 × 10−3 | 2.39 (1.15-4.99) | .02 | 1.81 (1.32-2.47) | 2.2 × 10−4 |
| rs11692304 | 103095404 | G/A | 0.47/0.48 | 1.61 (1.19-2.16) | 2 × 10−3 | 1.95 (1.03-3.7) | .041 | 1.66 (1.27-2.18) | 2.2 × 10−4 |
| rs13015714 | 102971865 | G/T | 0.77/0.76 | 1.79 (1.17-2.73) | 8 × 10−3 | 2.92 (1.22-6.97) | .016 | 1.96 (1.34-2.88) | 5.3 × 10−4 |
| rs72627435* | 102897739 | T/C | 0.21/0.20 | 1.76 (1.29-2.4) | 3.8 × 10−4 | 2.01 (1.09-3.69) | .024 | 1.81 (1.37-2.38) | 2.8 × 10−5 |
| rs4851005 | 103011552 | C/T | 0.37/0.34 | 1.85 (1.38-2.47) | 3.3 × 10−5 | 2.17 (1.15-4.09) | .017 | 1.9 (1.46-2.47) | 1.9 × 10−6 |
| rs13019803 | 102776202 | C/T | 0.08/0.08 | 2.31 (1.51-3.53) | 1.1 × 10−4 | 2.53 (1.11-5.77) | .028 | 2.35 (1.61-3.43) | 8.9 × 10−6 |
| rs4851601* | 103116261 | G/A | 0.28/0.26 | 2.01 (1.48-2.73) | 8.3 × 10−6 | 1.92 (1.03-3.6) | .042 | 1.99 (1.51-2.62) | 9.7 × 10−7 |
| Multiallele | — | GCG/TTA | 1.94 (1.54-2.44) | 1.8 × 10−8 | 2.24 (1.36-3.69) | .002 | 1.99 (1.61-2.45) | 1.2 × 10−10 | |
SNP associations with GVHD death are adjusted for AML diagnosis, recipient obesity (>30 mg/kg2), donor age, and peripheral blood cell source. SNP associations with infection death are adjusted for recipient age, advanced disease at HCT, and recipient and donor CMV status. For infection, we computed a multiallele model that included the clinical covariates plus a variable collapsing the SNPs shown in bold, such that recipients have between 0 and 6 donor risk alleles. For GVHD, SNPs showed some LD (r2 = 0.52) and were thus better markers alone than collectively. Cohort 1 (C1), n = 1584; cohort 2 (C2), n = 669.
hg19, position according to human reference genome version hg19; Ref, reference allele; Risk, risk allele.
SNP is imputed.