Replication of factors that showed a strong relationship with dose in the pilot cohort28
| Genetic variant or other factor . | Pilot cohort . | Replication cohort . | |||||
|---|---|---|---|---|---|---|---|
| N . | R2 . | P . | N . | R2 . | P . | ||
| VKORC1 | rs9923231 | 181 | 31.7% | 1.91 × 10−15 | 1293 | 29.3% | 1.03 × 10−97 |
| VKORC1 | rs2359612 | 200 | 29.0% | 2.30 × 10−15 | 1292 | 29.8% | 9.82 × 10−100 |
| CYP2C9 | *2 and *3 | 201 | 15.9% | 2.29 × 10−6 | 1321 | 11.8% | 6.63 × 10−34 |
| CYP2C9 | rs4917639 | 197 | 11.8% | 4.94 × 10−6 | 1092 | 11.7% | 4.61 × 10−30 |
| PROC | rs2069919 | 182 | 9.0% | 2.16 × 10−4 | 1294 | 0.2% | 2.07 × 10−1 |
| EPHX1 | rs4653436 | 196 | 4.8% | 8.48 × 10−3 | 1207 | 0.1% | 4.25 × 10−1 |
| GGCX* | rs12714145/rs7568458 | 198 | 3.4% | 3.32 × 10−2 | 1252 | 0.1% | 4.97 × 10−1 |
| ORM1 | rs1687390 | 149 | 2.6% | 4.96 × 10−2 | 1310 | 0% | 9.14 × 10−1 |
| Age | 201 | 9.2% | 1.20 × 10−5 | 1324 | 14.5% | 8.00 × 10−47 | |
| Sex | 201 | 2.6% | 2.29 × 10−2 | 1324 | 1.2% | 6.89 × 10−5 | |
| Interaction (increased INR) | 201 | 3.6% | 6.67 × 10−2 | 1324 | 1.5% | 8.00 × 10−6 | |
| Genetic variant or other factor . | Pilot cohort . | Replication cohort . | |||||
|---|---|---|---|---|---|---|---|
| N . | R2 . | P . | N . | R2 . | P . | ||
| VKORC1 | rs9923231 | 181 | 31.7% | 1.91 × 10−15 | 1293 | 29.3% | 1.03 × 10−97 |
| VKORC1 | rs2359612 | 200 | 29.0% | 2.30 × 10−15 | 1292 | 29.8% | 9.82 × 10−100 |
| CYP2C9 | *2 and *3 | 201 | 15.9% | 2.29 × 10−6 | 1321 | 11.8% | 6.63 × 10−34 |
| CYP2C9 | rs4917639 | 197 | 11.8% | 4.94 × 10−6 | 1092 | 11.7% | 4.61 × 10−30 |
| PROC | rs2069919 | 182 | 9.0% | 2.16 × 10−4 | 1294 | 0.2% | 2.07 × 10−1 |
| EPHX1 | rs4653436 | 196 | 4.8% | 8.48 × 10−3 | 1207 | 0.1% | 4.25 × 10−1 |
| GGCX* | rs12714145/rs7568458 | 198 | 3.4% | 3.32 × 10−2 | 1252 | 0.1% | 4.97 × 10−1 |
| ORM1 | rs1687390 | 149 | 2.6% | 4.96 × 10−2 | 1310 | 0% | 9.14 × 10−1 |
| Age | 201 | 9.2% | 1.20 × 10−5 | 1324 | 14.5% | 8.00 × 10−47 | |
| Sex | 201 | 2.6% | 2.29 × 10−2 | 1324 | 1.2% | 6.89 × 10−5 | |
| Interaction (increased INR) | 201 | 3.6% | 6.67 × 10−2 | 1324 | 1.5% | 8.00 × 10−6 | |
Univariate R2 values (percentage of dose variance explained) and P values from the pilot cohort and the replication (WARG) cohort are shown. In the replication cohort, 1324 patients with a minimum of 3 consecutive therapeutic INRs are taken into account. All genotyping results are used in the pilot cohort, which is separate from the replication cohort. N represents the number of patients with data for the factor in each study.
In the replication study GGCX rs7568458 was genotyped instead of rs12714145. They are in high LD.