Table 3.
Acute chest syndrome association results
| SNP | Chromosome (position) | Effect allele/other allele | Effect allele frequency | CSSCD discovery | CSSCD replication | Combined CSSCD | Georgia Health Sciences University | Duke | Gene (annotation) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β (SE) | P value | β (SE) | P value | β (SE) | P value | OR (95% CI) | P value | OR [95% CI] | P value | |||||
| rs10399947 | 1 (149128584) | A/G | 0.57 | −0.319 (0.082) | 1.2 × 10−4 | 0.339 (0.156) | .03 | −0.174 (0.073) | .02 | 0.98 [0.64, 1.50] | .93 | 0.89 [0.66, 1.21] | .47 | Intergenic |
| rs34661029 | 2 (61002492) | C/G | 0.98 | −0.822 (0.191) | 2.3 × 10−5 | −0.103 (0.450) | .82 | −0.709 (0.178) | 7.1 × 10−5 | 0.87 [0.24, 3.19] | .83 | 0.75 [0.16, 3.61] | .72 | REL (missense) |
| rs17749316 | 2 (191548954) | C/G | 0.99 | −0.891 (0.228) | 1.2 × 10−4 | 0.518 (1.013) | .61 | −0.821 (0.226) | 2.7 × 10−4 | 3.2 × 108 [0, inf] | 1.00 | 5.5 × 108 [0, inf] | 1.00 | STAT1 (intron) |
| rs13021001 | 2 (128125889) | A/G | 0.96 | −0.631 (0.149) | 3.0 × 10−5 | 0.450 (0.482) | .35 | −0.534 (0.144) | 2.1 × 10−4 | 0.55 [0.14, 2.19] | .39 | 0.84 [0.3, 2.34] | .73 | GPR17 (3′UTR) |
| rs6778854 | 3 (563448) | A/G | 0.61 | 0.374 (0.081) | 5.0 × 10−6 | 0.057 (0.161) | .72 | 0.309 (0.073) | 2.4 × 10−5 | 0.98 [0.64, 1.50] | .92 | NA | NA | Intergenic |
| rs13315133 | 3 (38624908) | A/C | 0.79 | −0.339 (0.082) | 4.3 × 10−5 | 0.031 (0.197) | .88 | −0.284 (0.076) | 2.0 × 10−4 | 0.90 [0.53, 1.54] | .71 | NA | NA | SCN5A (intron) |
| rs3910551 | 3 (106659325) | C/G | 0.02 | 0.793 (0.180) | 1.4 × 10−5 | −0.333 (0.532) | .53 | 0.675 (0.172) | 9.1 × 10−5 | 1.13 [0.38, 3.32] | .83 | 0.25 [0.08, 0.81] | .02 | ALCAM (intron) |
| rs5030094 | 3 (187943852) | T/C | 0.99 | −0.801 (0.221) | 3.5 × 10−4 | −0.727 (0.424) | .09 | −0.785 (0.198) | 7.5 × 10−5 | 0.54 [0.14, 2,15] | .38 | 0.73 [0.11, 4.71] | .74 | KNG1 (intron) |
| rs10478813 | 5 (127859164) | C/G | 0.16 | 0.400 (0.109) | 2.8 × 10−4 | −0.002 (0.240) | .99 | 0.330 (0.100) | 9.9 × 10−4 | 0.81 [0.38, 1.75] | .60 | NA | NA | FBN2 (intron) |
| rs5576 | 7 (24297876) | A/G | 0.97 | −0.655 (0.152) | 2.1 × 10−5 | 0.078 (0.477) | .87 | −0.586 (0.146) | 6.3 × 10−5 | 1.66 [0.37, 7.55] | .51 | 1.05 [0.37, 3.03] | .92 | NPY (3′UTR) |
| rs1176758 | 11 (113275565) | A/G | 0.92 | −0.528 (0.117) | 9.7 × 10−6 | 0.110 (0.275) | .69 | −0.427 (0.109) | 9.7 × 10−5 | 1.61 [0.49, 5.33] | .43 | 0.68 [0.33, 1.38] | .29 | Intergenic |
| rs6309 | 13 (46368601) | A/G | 0.04 | 0.631 (0.159) | 9.0 × 10−5 | −0.391 (0.477) | .41 | 0.526 (0.153) | 5.6 × 10−4 | 1.43 [0.45, 4.56] | .55 | 0.68 [0.34, 1.34] | .26 | HTR2A (intron) |
| rs9927848 | 16 (23740572) | A/C | 0.44 | −0.354 (0.099) | 4.3 × 10−4 | 0.317 (0.147) | .03 | −0.141 (0.083) | .09 | 1.14 [0.74, 1.75] | .55 | 1.03 [0.75, 1.40] | .87 | Intergenic |
| rs12447481 | 16 (52306470) | T/G | 0.98 | −0.794 (0.206) | 1.5 × 10−4 | −0.830 (0.450) | .07 | −0.800 (0.190) | 2.5 × 10−5 | 3.3 × 108 [0, inf] | 1 | 1.70 [0.31, 9.43] | .54 | FTO (intron) |
| rs6141803 | 20 (30804017) | T/C | 0.98 | −0.701 (0.171) | 5.4 × 10−5 | −0.797 (0.266) | .003 | −0.730 (0.145) | 5.2 × 10−7 | 0.41 [0.07, 2.34] | .32 | 0.16 [0.02, 1.23] | .08 | Intergenic |
| rs17728960 | 20 (49563123) | T/C | 0.98 | −0.789 (0.208) | 1.9 × 10−4 | −0.053 (0.354) | .88 | −0.595 (0.182) | 1.1 × 10−3 | 0.35 [0.12, 0.99] | .05 | 0.28 [0.04, 2.19] | .22 | NFATC2 (intron) |
| rs16998437 | 22 (36418341) | T/G | 0.92 | −0.483 (0.1216) | 9.3 × 10−5 | −0.061 (0.233) | .79 | 0.390 (0.109) | 3.5 × 10−4 | NA | NA | 1.07 [0.52, 2.18] | .86 | NOL12 (3′UTR) |
We genotyped 17 SNPs with P < 1 × 10−4 in the CSSCD Discovery dataset (before GC correction) in an independent subset of the CSSCD. We combined results from the discovery and replication CSSCD cohorts using an inverse variance meta-analysis approach. Only 1 SNP (rs6141803, in bold) replicated at nominal significance and reached array-wide significance (P < 2 × 10−6) in the combined analysis. We also report results for the analysis of acute chest syndrome as a dichotomous trait in the GHSU and Duke cohorts. For rs6141803, the association was not significant but trended in the right direction. P values for the CSSCD Discovery cohort are GC corrected. Genomic positions are on NCBI build 37.1.
NA, not available; SE, standard error.