Table 2.
Eight novel blood pressure loci reaching genome-wide significance (P<5×10−8) in meta-analysis according to GenSalt intervention phenotypes.
| Lead SNP | Chr | Position (bp) |
Nearest Gene |
Major Allele |
Minor Allele |
Study | No. | MAF | Systolic Blood Pressure | Diastolic Blood Pressure | Mean Arterial Pressure | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta (SE)* | P-value | Beta (SE)* | P-value | Beta (SE)* | P-value | |||||||||
| Blood Pressure During Low-Sodium Intervention | ||||||||||||||
| rs1330225 | 1 | 106637466 | PRMT6† | T | C | GenSalt | 1,881 | 0.01 | −6.23 (1.81) | 6.08E-04 | −6.39 (1.34) | 1.96E-06 | −6.35 (1.32) | 1.56E-06 |
| GenSalt Replication | 689 | 0.02 | −3.52 (1.74) | 4.33E-02 | −4.51 (1.37) | 1.12E-03 | −4.15 (1.21) | 7.08E-04 | ||||||
| Meta-analysis | 2,570 | 0.01 | −4.81 (1.25) | 1.22E-04 | −5.48 (0.96) | 1.08E-08 | −5.16 (0.89) | 7.29E-09 | ||||||
| rs10930597 | 2 | 174035091 | CDCA7 | C | T | GenSalt | 1,881 | 0.05 | −4.57 (0.97) | 3.08E-06 | −3.72 (0.73) | 4.25E-07 | −4.02 (0.71) | 2.05E-08 |
| GenSalt Replication | 689 | 0.05 | −1.52 (1.57) | 3.35E-01 | −1.56 (1.16) | 1.79E-01 | −1.54 (1.19) | 1.95E-01 | ||||||
| Meta-analysis | 2,570 | 0.05 | −3.72 (0.83) | 7.05E-06 | −3.11 (0.62) | 5.21E-07 | −3.37 (0.61) | 3.57E-08 | ||||||
| Blood Pressure Responses to Low-Sodium Intervention | ||||||||||||||
| rs8002688‡ | 13 | 72457983 | PIBF1 | C | T | GenSalt | 1881 | 0.04 | 2.03 (0.37) | 3.69E-08 | 0.56 (0.43) | 1.97E-01 | 1.04 (0.35) | 2.93E-03 |
| GenSalt Replication | 694 | 0.05 | 2.13 (0.91) | 1.94E-02 | 1.08 (0.73) | 1.38E-01 | 1.43 (0.71) | 4.63E-02 | ||||||
| Meta-analysis | 2,575 | 0.04 | 2.04 (0.34) | 1.78E-09 | 0.70 (0.37) | 6.16E-02 | 1.12 (0.31) | 3.75E-04 | ||||||
| Blood Pressure During High-Sodium Intervention | ||||||||||||||
| rs16890334 | 6 | 79612885 | IRAK1BP1 | T | C | GenSalt | 1881 | 0.06 | −6.00 (1.07) | 2.92E-08 | −2.15 (0.84) | 1.09E-02 | −3.46 (0.83) | 3.14E-05 |
| GenSalt Replication | 695 | 0.06 | −3.81 (1.81) | 3.58E-02 | −2.90 (1.31) | 2.80E-02 | −3.19 (1.43) | 2.59E-02 | ||||||
| Meta-analysis | 2,576 | 0.06 | −5.43 (0.92) | 4.23E-09 | −2.37 (0.71) | 8.43E-04 | −3.39 (0.72) | 2.17E-06 | ||||||
| Blood Pressure During Potassium Intervention | ||||||||||||||
| rs10930597 | 2 | 174035091 | CDCA7 | C | T | GenSalt | 1881 | 0.05 | −4.81 (1.02) | 2.92E-06 | −3.67 (0.68) | 8.07E-08 | −4.04 (0.70) | 1.21E-08 |
| GenSalt Replication | 689 | 0.05 | −1.66 (1.72) | 3.35E-01 | −1.88 (1.14) | 1.00E-01 | −1.82 (1.21) | 1.34E-01 | ||||||
| Meta-analysis | 2,570 | 0.05 | −3.99 (0.88) | 5.90E-06 | −3.20 (0.58) | 4.25E-08 | −3.48 (0.61) | 1.10E-08 | ||||||
| rs11887188§ | 2 | 234967549 | ARL4C | C | T | GenSalt | 1881 | 0.04 | −2.16 (1.02) | 3.45E-02 | −3.72 (0.68) | 4.80E-08 | −3.20 (0.71) | 7.03E-06 |
| GenSalt Replication§ | 691 | 0.03 | −2.93 (1.76) | 9.77E-02 | −2.02 (1.16) | 8.11E-02 | −2.31 (1.25) | 6.40E-02 | ||||||
| Meta-analysis | 2,572 | 0.03 | −2.35 (0.88) | 7.72E-03 | −3.28 (0.58) | 1.86E-08 | −2.98 (0.62) | 1.29E-06 | ||||||
| rs16890334 | 6 | 79612885 | IRAK1BP1 | T | C | GenSalt | 1881 | 0.06 | −5.70 (1.01) | 1.74E-08 | −1.98 (0.77) | 1.06E-02 | −3.22 (0.76) | 2.75E-05 |
| GenSalt Replication | 695 | 0.06 | −4.63 (1.52) | 2.53E-03 | −2.45 (1.03) | 1.76E-02 | −3.18 (1.14) | 5.72E-03 | ||||||
| Meta-analysis | 2,576 | 0.06 | −5.38 (0.84) | 1.44E-10 | −2.15 (0.62) | 5.02E-04 | −3.20 (0.64) | 4.55E-07 | ||||||
| rs2030114 | 16 | 50167448 | SALL1 | G | A | GenSalt | 1881 | 0.01 | −3.56 (1.56) | 2.27E-02 | −4.44 (0.85) | 1.75E-07 | −4.13 (0.99) | 3.15E-05 |
| GenSalt Replication | 685 | 0.01 | −6.91 (4.84) | 1.54E-01 | −2.67 (0.51) | 3.21E-07 | −4.10 (1.74) | 1.91E-02 | ||||||
| Meta-analysis | 2,566 | 0.01 | −3.87 (1.48) | 9.07E-03 | −3.14 (0.44) | 7.01E-13 | −4.12 (0.86) | 1.62E-06 | ||||||
| Blood Pressure Response to Cold Pressor Test (Time 0) | ||||||||||||||
| rs7577262 | 2 | 234483608 | TRPM8 | G | A | GenSalt | 1881 | 0.37 | −1.88 (0.35) | 9.47E-08 | −0.68 (0.23) | 2.56E-03 | −1.09 (0.23) | 2.70E-06 |
| GenSalt Replication | 688 | 0.36 | −1.14 (0.64) | 7.76E-02 | −0.49 (0.38) | 1.98E-01 | −0.71 (0.41) | 8.02E-02 | ||||||
| Meta-analysis | 2,569 | 0.37 | −1.71 (0.31) | 2.68E-08 | −0.63 (0.19) | 1.12E-03 | −1.00 (0.20) | 6.76E-07 | ||||||
| rs17135875‡ | 7 | 102306267 | FBXL13 | T | C | GenSalt | 1881 | 0.01 | −5.56 (1.15) | 1.66E-06 | −3.25 (0.64) | 5.39E-07 | −3.94 (0.65) | 1.53E-09 |
| GenSalt Replication | 686 | 0.02 | −2.06 (2.21) | 3.50E-01 | −0.87 (1.35) | 5.20E-01 | −1.27 (1.34) | 3.45E-01 | ||||||
| Meta-analysis | 2,567 | 0.01 | −4.81 (1.02) | 2.60E-06 | −2.81 (0.58) | 1.40E-06 | −3.44 (0.58) | 3.74E-09 | ||||||
Physical positions are listed according to NCBI build 36.3. Beta is the effect size per minor allele based on an additive genetic model. bp = basepairs; Chr = chromosome; Freq = frequency; SE = standard error; SNP = single nucleotide polymorphism.
*
Effect size in mm Hg.
†
Gene located over 500,000 bp away from the lead SNP.
‡
Lead SNP lays within the corresponding gene.
§
rs11692463 was used as a proxy for rs11887188 in the replication sample (r2=0.98).