Table 5. Top GWAS-identified SNPs associated with total morphine sulfate dose requirement in the African-American discovery cohort.
| SNP | Closest Gene | CHR | BP (hg18) | Minor/Major Allele | MAF | Beta | CI 95% | P-value |
|---|---|---|---|---|---|---|---|---|
| rs1875227 | MT4 | 16 | 55156116 | T/C | 0.015 | 60.09 | (36.68, 83.49) | 9.61×10-7 |
| rs1872270 | DMP1 | 4 | 88828705 | T/C | 0.34 | 16.33 | (9.742, 22.92) | 2.18×10-6 |
| rs1503245 | C1D | 2 | 68078248 | T/C | 0.060 | 31.39 | (18.55, 44.24) | 2.96×10-6 |
| rs10515902 | ODZ2 | 5 | 165002573 | A/G | 0.029 | 46.55 | (27.28, 65.82) | 3.80×10-6 |
| rs4620271 | CPA6 | 8 | 68904031 | T/C | 0.18 | 18.82 | (11.03, 26.62) | 3.86×10-6 |
| rs9457743 | PNLDC1 | 6 | 160193689 | G/T | 0.36 | -15.73 | (-22.44, -9.03) | 6.83×10-6 |
| rs6930229 | PNLDC1 | 6 | 160203429 | A/C | 0.36 | -15.63 | (-22.35, -8.91) | 8.22×10-6 |
| rs10915528 | AJAP1 | 1 | 4371234 | C/T | 0.075 | 27.88 | (15.88, 39.89) | 8.46×10-6 |
| rs2869703 | DMP1 | 4 | 88845302 | C/T | 0.29 | 16.56 | (9.44, 23.69) | 8.50×10-6 |
| rs12566055 | USP24 | 1 | 56033402 | T/C | 0.012 | 67.45 | (38.37, 96.53) | 8.74×10-6 |
| rs234348 | PSMC4 | 19 | 45159823 | G/A | 0.21 | 18.28 | (10.34, 26.21) | 1.00×10-5 |
| rs1106561 | IGSF9B | 11 | 133282598 | C/T | 0.017 | 51.82 | (29.26, 74.38) | 1.06×10-5 |
| rs329665 | IGSF9B | 11 | 133262385 | T/C | 0.017 | 51.82 | (29.26, 74.38) | 1.06×10-5 |
| rs7996854 | SPRY2 | 13 | 80075599 | A/G | 0.14 | 19.84 | (10.92, 28.75) | 1.93×10-5 |
| rs2052369 | KCNMB2 | 3 | 179226332 | C/T | 0.15 | 20.03 | (11.02, 29.04) | 1.96×10-5 |
| rs5921071 | DIAPH2 | 23 | 97524912 | A/G | 0.17 | 21.13 | (11.61, 30.66) | 2.03×10-5 |
| rs2629812 | SYT6 | 1 | 114454559 | G/A | 0.40 | 14.12 | (7.69, 20.56) | 2.50×10-5 |
| rs726403 | TGM3 | 20 | 2154591 | G/T | 0.040 | 35.11 | (19.1, 51.12) | 2.52×10-5 |
| rs4238351 | RORA | 15 | 59231778 | G/A | 0.47 | -14.89 | (-21.68, -8.09) | 2.56×10-5 |
| rs2268550 | TBX19 | 1 | 166615795 | A/G | 0.18 | 18.36 | (9.97, 26.75) | 2.62×10-5 |
| rs11997612 | SGCZ | 8 | 14246099 | C/T | 0.16 | -20.72 | (-30.24, -11.2) | 2.90×10-5 |
| rs10770826 | PEX5 | 12 | 7276760 | A/G | 0.41 | -14.05 | (-20.54, -7.57) | 3.14×10-5 |
| rs11157432 | FANCM | 14 | 44688967 | G/A | 0.017 | 55.09 | (29.56, 80.62) | 3.36×10-5 |
| rs16859092 | NOS1AP | 1 | 160491174 | C/T | 0.083 | -25.57 | (-37.42, -13.72) | 3.36×10-5 |
| rs2473594 | LRFN2 | 6 | 40658416 | T/C | 0.32 | 15.48 | (8.29, 22.68) | 3.54×10-5 |
| rs16851279 | ALCAM | 3 | 106748964 | C/T | 0.081 | 23.7 | (12.64, 34.76) | 3.80×10-5 |
| rs2195349 | COX7C | 5 | 85978500 | C/T | 0.10 | 20.59 | (10.92, 30.27) | 4.24×10-5 |
| rs2959777 | MCph1 | 8 | 6421343 | G/A | 0.48 | 14.04 | (7.43, 20.65) | 4.46×10-5 |
| rs2191888 | NEUROD6 | 7 | 31349029 | C/A | 0.093 | 23.45 | (12.36, 34.54) | 4.76×10-5 |
| rs717252 | LPHN3 | 4 | 60846313 | C/T | 0.40 | -14.06 | (-20.72, -7.40) | 4.84×10-5 |
Reported SNPs limited to those with p<5×105 for the primary outcome of total morphine sulfate dose in the 241 subject discovery cohort of African-American ancestry with full phenotype. A= adenine, Beta = regression coefficient in mcg/kg morphine, BP = base pairs, C = cytosine, CHR = chromosome, CI 95% = 95% confidence interval, G = guanine, GWAS = genome-wide association study, MAF = minor allele frequency, SNP = single nucleotide polymorphism, T = thymine.