Effect sizes and P values for the well-established warfarin-related SNPs
| rsID (reference/alternative alleles) . | Common name . | CHR . | Position∗ . | All cohorts (METAL) . | All cohorts (African tracts, METAL) . | All cohorts (MR-MEGA)† . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Common MAF (%) . | β‡ (SE) . | P . | Direction§ . | Het I2 . | Change in warfarin dose‖ (%) . | Common MAF (%) . | β‡ (SE) . | P . | Direction§ . | Het I2 . | Change in warfarin dose‖ (%) . | Common MAF (%) . | P . | Direction§ . | ||||
| rs7900194 (G/A) | CYP2C9∗8 | 10 | 96702066 | 0.075 | −0.421 (0.070) | 1.63E−09 | −−+−−− | 36.8 | 34.4 | 0.081 | −0.365 (0.064) | 9.19E−09 | −−−−−− | 0.0 | 30.6 | 0.070 | 8.62E−08 | −−+−−− |
| rs2256871 (A/G) | CYP2C9∗9 | 10 | 96708974 | 0.134 | −0.141 (0.054) | 9.29E−03 | −−−−−− | 0.0 | 13.1 | 0.137 | −0.119 (0.051) | 1.93E−02 | −−−−+− | 0.0 | 11.2 | 0.117 | 1.18E−01 | −−−−−− |
| rs28371685 (C/T) | CYP2C9∗11 | 10 | 96740981 | 0.023 | −0.393 (0.126) | 1.77E−03 | −−−−−− | 0.0 | 32.5 | 0.028 | −0.286 (0.110) | 9.64E−03 | −−−−−− | 0.0 | 24.9 | 0.020 | 1.16E−02 | −−−−−− |
| rs12777823 (G/A) | rs12777823 (G>A) | 10 | 96405502 | 0.274 | −0.229 (0.039) | 4.86E−09 | −−++−− | 75.7 | 20.5 | 0.284 | −0.230 (0.037) | 7.75E−10 | −−+−−− | 38.7 | 20.5 | 0.274 | 7.94E−11 | −−++−− |
| rs7294 (G/A) | VKORC1 3730G>A | 16 | 31102321 | 0.470 | 0.148 (0.036) | 3.60E−05 | ++++++ | 68.8 | 15.9 | 0.473 | 0.089 (0.035) | 9.56E−03 | +++−++ | 0.4 | 9.4 | 0.471 | 1.96E−06 | ++++++ |
| rs2359612 (C/T) | VKORC1 2255C>T | 16 | 31103796 | 0.240 | 0.191 (0.041) | 3.01E−06 | +++−++ | 62.6 | 21.0 | 0.207 | 0.115 (0.042) | 6.00E−03 | +++−++ | 0.0 | 12.2 | 0.233 | 8.21E−07 | +++−++ |
| rs8050894 (G/C) | VKORC1 1542G>C | 16 | 31104509 | 0.256 | −0.211 (0.041) | 2.63E−07 | −−−−−− | 60.4 | 19.0 | 0.229 | −0.106 (0.041) | 1.03E−02 | −−−−+− | 0.0 | 10.0 | 0.248 | 1.52E−07 | −−−−−− |
| rs9934438 (C/T) | VKORC1 1173C>T | 16 | 31104878 | 0.141 | −0.495 (0.062) | 1.21E−15 | −−−−−− | 0.0 | 39.0 | 0.052 | −0.449 (0.080) | 1.56E−08 | −−−−−− | 9.7 | 36.2 | 0.093 | 1.25E−13 | −−−−−− |
| rs9923231 (G/A) | VKORC1 -1639G>A | 16 | 31107689 | 0.141 | −0.496 (0.062) | 1.24E−15 | −−−−−− | 0.0 | 39.1 | 0.052 | −0.450 (0.080) | 1.60E−08 | −−−−−− | 9.4 | 36.2 | 0.093 | 1.29E−13 | −−−−−− |
| rsID (reference/alternative alleles) . | Common name . | CHR . | Position∗ . | All cohorts (METAL) . | All cohorts (African tracts, METAL) . | All cohorts (MR-MEGA)† . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Common MAF (%) . | β‡ (SE) . | P . | Direction§ . | Het I2 . | Change in warfarin dose‖ (%) . | Common MAF (%) . | β‡ (SE) . | P . | Direction§ . | Het I2 . | Change in warfarin dose‖ (%) . | Common MAF (%) . | P . | Direction§ . | ||||
| rs7900194 (G/A) | CYP2C9∗8 | 10 | 96702066 | 0.075 | −0.421 (0.070) | 1.63E−09 | −−+−−− | 36.8 | 34.4 | 0.081 | −0.365 (0.064) | 9.19E−09 | −−−−−− | 0.0 | 30.6 | 0.070 | 8.62E−08 | −−+−−− |
| rs2256871 (A/G) | CYP2C9∗9 | 10 | 96708974 | 0.134 | −0.141 (0.054) | 9.29E−03 | −−−−−− | 0.0 | 13.1 | 0.137 | −0.119 (0.051) | 1.93E−02 | −−−−+− | 0.0 | 11.2 | 0.117 | 1.18E−01 | −−−−−− |
| rs28371685 (C/T) | CYP2C9∗11 | 10 | 96740981 | 0.023 | −0.393 (0.126) | 1.77E−03 | −−−−−− | 0.0 | 32.5 | 0.028 | −0.286 (0.110) | 9.64E−03 | −−−−−− | 0.0 | 24.9 | 0.020 | 1.16E−02 | −−−−−− |
| rs12777823 (G/A) | rs12777823 (G>A) | 10 | 96405502 | 0.274 | −0.229 (0.039) | 4.86E−09 | −−++−− | 75.7 | 20.5 | 0.284 | −0.230 (0.037) | 7.75E−10 | −−+−−− | 38.7 | 20.5 | 0.274 | 7.94E−11 | −−++−− |
| rs7294 (G/A) | VKORC1 3730G>A | 16 | 31102321 | 0.470 | 0.148 (0.036) | 3.60E−05 | ++++++ | 68.8 | 15.9 | 0.473 | 0.089 (0.035) | 9.56E−03 | +++−++ | 0.4 | 9.4 | 0.471 | 1.96E−06 | ++++++ |
| rs2359612 (C/T) | VKORC1 2255C>T | 16 | 31103796 | 0.240 | 0.191 (0.041) | 3.01E−06 | +++−++ | 62.6 | 21.0 | 0.207 | 0.115 (0.042) | 6.00E−03 | +++−++ | 0.0 | 12.2 | 0.233 | 8.21E−07 | +++−++ |
| rs8050894 (G/C) | VKORC1 1542G>C | 16 | 31104509 | 0.256 | −0.211 (0.041) | 2.63E−07 | −−−−−− | 60.4 | 19.0 | 0.229 | −0.106 (0.041) | 1.03E−02 | −−−−+− | 0.0 | 10.0 | 0.248 | 1.52E−07 | −−−−−− |
| rs9934438 (C/T) | VKORC1 1173C>T | 16 | 31104878 | 0.141 | −0.495 (0.062) | 1.21E−15 | −−−−−− | 0.0 | 39.0 | 0.052 | −0.449 (0.080) | 1.56E−08 | −−−−−− | 9.7 | 36.2 | 0.093 | 1.25E−13 | −−−−−− |
| rs9923231 (G/A) | VKORC1 -1639G>A | 16 | 31107689 | 0.141 | −0.496 (0.062) | 1.24E−15 | −−−−−− | 0.0 | 39.1 | 0.052 | −0.450 (0.080) | 1.60E−08 | −−−−−− | 9.4 | 36.2 | 0.093 | 1.29E−13 | −−−−−− |
Data shown for n = 1504. Only SNPs present in all 6 cohorts were pooled during meta-analysis.
Gene names are italicized whereas P values passing the genome-wide significance threshold of P < 5 × 10−8 are italicized and bolded.
CYP, cytochrome P450; Het I2, heterogeneity I2 statistic; NA, not applicable; rsID, reference SNP cluster ID; SE, standard error; VKORC1, vitamin K epoxide reductase complex, subunit 1.
Human assembly GRCh37 (hg19).
No β (SE) and Het I2 values reported for MR-MEGA.
Coefficient of the alternative allele relative to the reference allele.
Each symbol represents a cohort in the order War-PATH cohort 1, War-PATH cohort 2, War-PATH cohort 3, War-PATH cohort 4, IWPC cohort, and UAB cohort (see Table 1; supplemental Table 15 for details). The “+” and “−“ directions indicate increased and decreased weekly warfarin doses, respectively, in the individual included cohorts.
Computed from the log-transformed betas using the formula: absolute(exp(β) − 1) × 100. A corresponding negative (positive), β means the variant will decrease (increase) weekly warfarin dose by the computed percentage.