Table 3.
SNPs associated disease severity at FDR less than 0.02
| Disease Severity | HbF% | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SNP | Chr | BP | Gene | Min | Maj | MAF | OR | P | Bonf | FDR | Beta | SE | P | Var |
| rs483850 | 1 | 203478366 | FAIM3 | T | A | 0.45 | 0.65 | 9.7E-04 | 7.3E-01 | 0.01 | 0.05 | .05 | 0.10 | .52 |
| rs934956 | 2 | 104555647 | Intergenic | T | C | 0.17 | 1.93 | 5.6E-04 | 4.2E-01 | 0.01 | 0.00 | .05 | 0.97 | .40 |
| rs370898 | 3 | 21442705 | ZNF659 | G | T | 0.05 | 0.37 | 1.4E-03 | 1 | 0.01 | 0.01 | .05 | 0.93 | .32 |
| rs903047 | 3 | 132234707 | NEK11 | T | C | 0.35 | 1.58 | 1.5E-03 | 1 | 0.01 | -0.03 | .05 | 0.44 | .30 |
| rs6443662 | 3 | 180834067 | Intergenic | C | T | 0.29 | 0.58 | 3.8E-04 | 2.8E-01 | 0.005 | 0.02 | .05 | 0.57 | .30 |
| rs950310 | 4 | 9519119 | SLC2A9 | A | T | 0.17 | 2.03 | 3.5E-04 | 2.6E-01 | 0.005 | -0.08 | .05 | 0.18 | .29 |
| rs258824 | 5 | 142577483 | ARHGAP26 | A | G | 0.39 | 1.58 | 1.1E-03 | 8.3E-01 | 0.01 | -0.06 | .05 | 0.12 | .29 |
| rs234915 | 6 | 2154576 | GMDS | A | C | 0.21 | 0.52 | 1.3E-04 | 9.5E-02 | 0.002 | 0.03 | .05 | 0.45 | .27 |
| rs545537 | 6 | 117751734 | ROS1 | A | G | 0.17 | 1.90 | 8.4E-04 | 6.3E-01 | 0.01 | 0.03 | .04 | 0.59 | .27 |
| rs4376364 | 6 | 135349178 | HBS1L | G | T | 0.34 | 1.70 | 4.3E-04 | 3.2E-01 | 0.01 | -0.07 | .05 | 0.10 | .27 |
| rs7804867 | 7 | 102627708 | SLC26A5 | A | G | 0.28 | 1.76 | 3.4E-04 | 2.6E-01 | 0.005 | -0.03 | .05 | 0.51 | .27 |
| rs6972505 | 7 | 102657988 | SLC26A5 | C | G | 0.24 | 2.13 | 7.6E-06 | 5.8E-03 | 0.0001 | -0.04 | .05 | 0.35 | .27 |
| rs1563408 | 7 | 113897140 | FOXP2 | G | A | 0.49 | 1.63 | 4.1E-04 | 3.1E-01 | 0.01 | 0.02 | .05 | 0.52 | .27 |
| rs766003 | 9 | 69709994 | c9orf135 | G | A | 0.16 | 0.52 | 2.6E-04 | 1.9E-01 | 0.004 | 0.04 | .05 | 0.37 | .25 |
| rs7936823 | 11 | 5206792 | Intergenic | C | T | 0.42 | 0.23 | 2.0E-11 | 1.5E-08 | <.0001 | 0.10 | .05 | 0.04 | .25 |
| rs6578588 | 11 | 5208867 | Intergenic | A | G | 0.42 | 0.21 | 1.2E-11 | 9.0E-09 | <.0001 | 0.09 | .05 | 0.07 | .24 |
| rs3813727 | 11 | 5212511 | HBD | T | C | 0.42 | 0.24 | 8.6E-11 | 6.5E-08 | <.0001 | 0.10 | .05 | 0.04 | .23 |
| rs3759074 | 11 | 5214371 | Intergenic | T | C | 0.41 | 0.18 | 3.6E-13 ± | 2.7E-10 | <.0001 | 0.10 | .05 | 0.05 | .23 |
| rs10837643 | 11 | 5214635 | Intergenic | A | T | 0.43 | 0.22 | 5.4E-10 | 4.1E-07 | <.0001 | 0.14 | .05 | 0.002 | .23 |
| rs4320977 | 11 | 5214758 | Intergenic | T | C | 0.42 | 0.23 | 1.6E-11 | 1.2E-08 | <.0001 | 0.10 | .05 | 0.04 | .22 |
| rs3759073 | 11 | 5214862 | Intergenic | A | G | 0.42 | 0.22 | 2.5E-11 | 1.9E-08 | <.0001 | 0.09 | .05 | 0.07 | .22 |
| rs4402323 | 11 | 5215185 | Intergenic | G | A | 0.42 | 0.22 | 4.5E-12 | 3.4E-09 | <.0001 | 0.10 | .05 | 0.04 | .22 |
| rs4910543 | 11 | 5215423 | Intergenic | C | G | 0.42 | 0.22 | 5.8E-12 | 4.4E-09 | <.0001 | 0.10 | .05 | 0.04 | .22 |
| rs2105819 | 11 | 5216332 | Intergenic | C | G | 0.42 | 0.24 | 4.9E-11 | 3.7E-08 | <.0001 | 0.11 | .05 | 0.03 | .22 |
| rs10128556 | 11 | 5220248 | HBBP1 | A | G | 0.42 | 0.20 | 3.4E-13 | 2.6E-10 | <.0001 | 0.10 | .05 | 0.05 | .21 |
| rs2071348 | 11 | 5220725 | HBBP1 | C | A | 0.41 | 0.19 | 4.8E-13 | 3.6E-10 | <.0001 | 0.09 | .05 | 0.07 | .21 |
| rs11036431 | 11 | 5222255 | HBBP1 | T | C | 0.43 | 0.23 | 6.3E-12 | 4.8E-09 | <.0001 | 0.08 | .05 | 0.10 | .20 |
| rs916111 | 11 | 5225911 | HBG1 | A | T | 0.43 | 0.23 | 1.7E-11 | 1.3E-08 | <.0001 | 0.10 | .05 | 0.04 | .20 |
| rs2855038 | 11 | 5228721 | HBG1 | A | G | 0.43 | 0.24 | 4.5E-12 | 3.4E-09 | <.0001 | 0.10 | .05 | 0.04 | .19 |
| rs2855036 | 11 | 5229250 | HBG2 | A | G | 0.41 | 0.20 | 3.5E-13 | 2.6E-10 | <.0001 | 0.09 | .05 | 0.08 | .19 |
| rs2855126 | 11 | 5229721 | HBG2 | G | C | 0.43 | 0.24 | 7.0E-12 | 5.3E-09 | <.0001 | 0.10 | .05 | 0.03 | .18 |
| rs2855125 | 11 | 5230257 | HBG2 | A | C | 0.43 | 0.25 | 1.2E-11 | 8.8E-09 | <.0001 | 0.12 | .04 | 0.01 | .18 |
| rs2236794 | 11 | 5230843 | HBG2 | G | A | 0.42 | 0.24 | 2.5E-11 | 1.9E-08 | <.0001 | 0.09 | .05 | 0.07 | .17 |
| rs2070972 | 11 | 5231293 | HBG2 | T | G | 0.43 | 0.24 | 3.6E-12 | 2.7E-09 | <.0001 | 0.10 | .03 | 0.04 | .16 |
| rs2187608 | 11 | 5231423 | HBG2 | G | C | 0.41 | 0.20 | 7.0E-13 | 5.3E-10 | <.0001 | 0.09 | .04 | 0.06 | .16 |
| rs2070973 | 11 | 5231985 | HBG2 | A | G | 0.44 | 0.23 | 5.6E-12 | 4.2E-09 | <.0001 | 0.09 | .05 | 0.06 | .16 |
| rs7482144 (XmnI) | 11 | 5232745 | HBG2 | T | C | 0.42 | 0.20 | 3.7E-13 | 2.8E-10 | <.0001 | 0.07 | .05 | 0.17 | .15 |
| rs2011051 | 11 | 5233395 | HBG2 | C | A | 0.43 | 0.24 | 1.2E-11 | 9.1E-09 | <.0001 | 0.09 | .05 | 0.07 | .15 |
| rs2855123 | 11 | 5233652 | HBG2 | T | A | 0.44 | 0.24 | 4.9E-11 | 3.7E-08 | <.0001 | 0.07 | .05 | 0.14 | .14 |
| rs2855121 | 11 | 5233869 | HBG2 | A | G | 0.41 | 0.20 | 2.2E-12 | 1.7E-09 | <.0001 | 0.08 | .05 | 0.12 | .12 |
| rs10160820 | 11 | 5239027 | Intergenic | G | T | 0.42 | 0.19 | 4.7E-13 | 3.6E-10 | <.0001 | 0.09 | .05 | 0.09 | .12 |
| rs7480802 | 11 | 5239080 | Intergenic | A | G | 0.43 | 0.24 | 2.1E-11 | 1.6E-08 | <.0001 | 0.09 | .05 | 0.07 | .11 |
| rs10160747 | 11 | 5240751 | Intergenic | A | G | 0.42 | 0.20 | 1.5E-12 | 1.2E-09 | <.0001 | 0.09 | .06 | 0.08 | .11 |
| rs10837707 | 11 | 5243234 | HBE1 | A | G | 0.43 | 0.22 | 1.4E-12 | 1.0E-09 | <.0001 | 0.09 | .05 | 0.07 | .11 |
| rs4910740 | 11 | 5243705 | HBE1 | C | T | 0.42 | 0.21 | 9.9E-13 | 7.5E-10 | <.0001 | 0.10 | .05 | 0.06 | .11 |
| bg200 * | 11 | 5245549 | HBE1 | T | G | 0.41 | 0.18 | 2.6E-13 | 2.0E-10 | <.0001 | 0.10 | .04 | 0.07 | .10 |
| rs3834466 | 11 | 5247976 | HBE1 | C | A | 0.42 | 0.23 | 1.7E-11 | 1.2E-08 | <.0001 | 0.07 | .05 | 0.13 | .10 |
| rs3759070 | 11 | 5248038 | HBE1 | C | G | 0.41 | 0.21 | 1.5E-12 | 1.1E-09 | <.0001 | 0.08 | .04 | 0.09 | .08 |
| rs3759069 | 11 | 5248240 | HBE1 | T | C | 0.43 | 0.23 | 3.1E-12 | 2.4E-09 | <.0001 | 0.09 | .06 | 0.06 | .08 |
| rs11036562 | 11 | 5250549 | HBE1 | G | T | 0.48 | 0.38 | 2.7E-08 | 2.0E-05 | <.0001 | 0.07 | .05 | 0.12 | .08 |
| rs11036634 | 11 | 5265154 | Intergenic | A | G | 0.50 | 2.34 | 1.4E-06 | 1.0E-03 | <.0001 | -0.02 | .06 | 0.65 | .07 |
| bg12 * | 11 | 5266933 | Intergenic | G | T | 0.49 | 2.31 | 6.8E-07 | 5.1E-04 | <.0001 | -0.06 | .05 | 0.20 | .06 |
| rs11036639 | 11 | 5267001 | Intergenic | C | T | 0.46 | 0.34 | 6.0E-09 | 4.5E-06 | <.0001 | 0.06 | .04 | 0.21 | .06 |
| rs11036641 | 11 | 5267496 | Intergenic | A | T | 0.49 | 2.26 | 2.6E-06 | 2.0E-03 | <.0001 | -0.06 | .04 | 0.21 | .06 |
| rs11036644 | 11 | 5268836 | Intergenic | C | T | 0.49 | 2.26 | 1.5E-06 | 1.2E-03 | <.0001 | -0.06 | .05 | 0.18 | .06 |
| rs4601817 | 11 | 5268977 | Intergenic | G | A | 0.49 | 2.25 | 1.8E-06 | 1.4E-03 | <.0001 | -0.07 | .05 | 0.17 | .06 |
| bg7 * | 11 | 5270798 | Intergenic | G | A | 0.46 | 0.40 | 2.4E-07 | 1.8E-04 | <.0001 | 0.05 | .04 | 0.26 | .06 |
| rs7933082 | 11 | 5273186 | Intergenic | C | G | 0.48 | 0.47 | 1.5E-05 | 1.2E-02 | 0.0002 | 0.05 | .04 | 0.36 | .05 |
| rs3888708 | 11 | 5274839 | Intergenic | T | G | 0.50 | 1.98 | 5.9E-05 | 4.5E-02 | 0.0009 | -0.03 | .04 | 0.47 | .05 |
| rs6578598 | 11 | 5275670 | Intergenic | T | C | 0.48 | 0.47 | 1.1E-05 | 8.4E-03 | 0.0002 | 0.04 | .05 | 0.41 | .05 |
| rs10837774 | 11 | 5279964 | OR51B4 | A | G | 0.45 | 0.38 | 7.3E-08 | 5.5E-05 | <.0001 | 0.05 | .04 | 0.32 | .04 |
| rs3886223 | 11 | 5300323 | OR51B2 | T | G | 0.42 | 0.33 | 3.7E-11 ± | 2.8E-08 | <.0001 | -0.01 | .04 | 0.83 | .04 |
| rs2030090 | 11 | 5430669 | OR51I2 | G | A | 0.22 | 1.81 | 1.5E-03 | 1 | 0.01 | 0.04 | .05 | 0.46 | .04 |
| rs449937 | 11 | 5446921 | OR51A10P | C | T | 0.16 | 2.08 | 5.2E-04 ± | 3.9E-01 | 0.01 | -0.03 | .05 | 0.64 | .03 |
| rs366257 | 11 | 5447119 | OR51A10P | G | A | 0.16 | 2.21 | 2.3E-04 ± | 1.7E-01 | 0.003 | -0.03 | .04 | 0.58 | .03 |
| rs446541 | 11 | 5448876 | OR51A10P | A | T | 0.26 | 0.48 | 2.5E-05 | 1.9E-02 | 0.0004 | 0.002 | .07 | 0.96 | .03 |
| rs678343 | 11 | 64728207 | CAPN1 | G | C | 0.37 | 1.63 | 7.1E-04 ± | 5.3E-01 | 0.01 | 0.04 | .04 | 0.26 | .03 |
| rs593753 | 11 | 72369088 | FCHSD2 | T | C | 0.29 | 0.60 | 6.5E-04 ± | 4.9E-01 | 0.01 | 0.05 | .04 | 0.21 | .02 |
| rs638135 | 11 | 85863336 | ME3 | A | G | 0.23 | 0.59 | 1.1E-03 ± | 8.3E-01 | 0.01 | 0.04 | .06 | 0.32 | .02 |
| rs632538 | 11 | 85869341 | ME3 | G | A | 0.25 | 0.60 | 1.5E-03 ± | 1 | 0.01 | 0.04 | .06 | 0.35 | .02 |
| rs2580874 | 12 | 8650077 | AICDA | G | A | 0.20 | 0.54 | 4.5E-04 | 3.4E-01 | 0.01 | 0.09 | .05 | 0.04 | .02 |
| rs1045411 | 13 | 29931232 | HMGB1 | A | G | 0.29 | 0.58 | 3.9E-04 | 2.9E-01 | 0.005 | 0.02 | .05 | 0.70 | .01 |
| rs886599 | 14 | 70244197 | Intergenic | A | G | 0.10 | 2.70 | 1.2E-04 | 9.0E-02 | 0.002 | 0.04 | .08 | 0.64 | .01 |
| rs1160027 | 17 | 51173101 | Intergenic | T | G | 0.20 | 0.56 | 8.5E-04 | 6.4E-01 | 0.01 | -0.01 | .06 | 0.79 | .01 |
| rs953695 | 18 | 59541550 | SERPINB11 | T | G | 0.21 | 1.83 | 7.6E-04 | 5.8E-01 | 0.01 | -0.03 | .04 | 0.63 | .01 |
| rs243341 | 19 | 4356106 | CHAF1A | T | C | 0.41 | 1.59 | 1.5E-03 | 1 | 0.01 | -0.04 | .04 | 0.33 | .00 |
| rs379327 | 19 | 61061978 | NLRP4 | A | G | 0.15 | 1.97 | 7.8E-04 | 5.9E-01 | 0.01 | -0.07 | .04 | 0.26 | .00 |
| rs639763 | 20 | 33325318 | MMP24 | T | C | 0.30 | 0.57 | 3.9E-04 | 2.9E-01 | 0.005 | -0.04 | .07 | 0.35 | .00 |
| rs6625978 | X | 71201690 | PIN4 | C | A | 0.06 | 3.35 | 1.3E-03 | 1 | 0.01 | -0.001 | .04 | 1.00 | .00 |
BP = location of SNP in base pairs in NCBI build 36
Min = Minor allele
Maj = Major allele
Beta = Absolute change in HbF% on the log scale per copy of the minor allele
SE = Standard error of the Beta estimate
Bonf = Bonferroni adjusted P --value
FDR = false discovery rate
MAF = minor allele frequency
* = SNP not in NCBI database
± = Chromosome 11 SNPs associated with disease severity at P < 0.05 after adjustment for Xmn1
SNPs significantly associated with disease severity after Bonferroni correction are in bold
P-values for SNPs associated with HbF% at P ≤ 0.05 in the mild disease group are in bold
SNPs in italics were previously shown to be associated with disease severity in this sample by Ma et al. 2007 [19]
Var = Percent of the variation in log transformed HbF% explained by each SNP