Single-variant meta-analysis results for hemostatic factors fibrinogen, FVII, FVIII, and vWF
| Factor and variant . | AA Change*† . | Gene . | Ancestry . | No. of participants in study . | MAF‡ . | β . | P . |
|---|---|---|---|---|---|---|---|
| Fibrinogen | |||||||
| rs201909029 (new) | K178N (K148N) | FGB | ALL | 76 316 | 7.7E-04 | −0.139 | 3.2E-13 |
| EUR | 65 733 | 8.8E-04 | −0.139 | 5.2E-13 | |||
| AFR | 8 388 | 6.0E-05 | −0.163 | 4.3E-01 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 3.5E-04 | −0.117 | 5.5E-01 | |||
| rs6054 | P265L (P235L) | FGB | ALL | 76 316 | 4.2E-03 | −0.111 | 1.8E-43 |
| EUR | 65 733 | 4.7E-03 | −0.111 | 3.7E-42 | |||
| AFR | 8 388 | 1.2E-03 | −0.104 | 2.6E-02 | |||
| ASI | 764 | 1.3E-03 | −0.130 | 3.0E-01 | |||
| HIS | 1 431 | 0 | NA | NA | |||
| rs145051028 (new) | S245F (S219F) | FGG | ALL | 76 316 | 1.6E-04 | −0.239 | 4.8E-09 |
| EUR | 65 733 | 0 | NA | NA | |||
| AFR | 8 388 | 1.5E-03 | −0.239 | 4.8E-09 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 0 | NA | NA | |||
| rs148685782 | A108G (A82G) | FGG | ALL | 76 316 | 3.3E-03 | −0.238 | 9.2E-152 |
| EUR | 65 733 | 3.8E-03 | −0.239 | 2.3E-150 | |||
| AFR | 8 388 | 4.2E-04 | −0.165 | 3.4E-02 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 3.5E-04 | −0.347 | 7.7E-02 | |||
| rs10479001 | A225V | PDLIM4 | ALL | 76 316 | 5.5E-02 | 0.013 | 1.3E-08 |
| EUR | 65 733 | 4.5E-02 | 0.018 | 4.3E-11 | |||
| AFR | 8 388 | 1.4E-01 | −0.001 | 8.3E-01 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 5.5E-02 | 0.019 | 2.3E-01 | |||
| rs1800961 | T117I | HNF4A | ALL | 76 316 | 2.7E-02 | −0.020 | 2.3E-10 |
| T139I | EUR | 65 733 | 3.0E-02 | −0.020 | 5.5E-10 | ||
| T169I | AFR | 8 388 | 5.9E-03 | 0.012 | 5.5E-01 | ||
| ASI | 764 | 1.1E-02 | −0.031 | 4.8E-01 | |||
| HIS | 1 431 | 4.2E-02 | −0.038 | 4.0E-02 | |||
| rs151272083 (new) | R865Q | KCNT1 | ALL | 76 316 | 2.2E-03 | 0.007 | 5.3E-01 |
| R877Q | EUR | 65 733 | 2.4E-03 | 0.017 | 1.3E-01 | ||
| R891Q | AFR | 8 388 | 7.2E-04 | −0.330 | 2.7E-07 | ||
| R910Q | ASI | 764 | 0 | NA | NA | ||
| HIS | 1 431 | 0 | NA | NA | |||
| rs141869748 (new) | I193T | HID1 | ALL | 76 316 | 1.6E-04 | −0.216 | 4.2E-07 |
| I421T | EUR | 65 733 | 0 | NA | NA | ||
| AFR | 8 388 | 1.3E-03 | −0.252 | 4.0E-08 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 1.1E-03 | 0.008 | 9.4E-01 | |||
| FVII | |||||||
| rs150525536 (new) | R117Q | F7 | ALL | 25 372 | 9.5E-04 | −31.44 | 1.8E-17 |
| R70Q | EUR | 20 401 | 9.8E-05 | −13.92 | 2.2E-01 | ||
| R139Q | AFR | 4 971 | 4.4E-03 | −33.56 | 9.7E-18 | ||
| rs121964926 (new) | R342Q | F7 | ALL | 25 372 | 1.2E-03 | −25.02 | 1.3E-14 |
| R295Q | EUR | 20 401 | 4.2E-04 | −0.52 | 9.3E-01 | ||
| R364Q | AFR | 4 971 | 4.4E-03 | −38.08 | 2.8E-21 | ||
| rs3093248 (new) | E423K | F7 | ALL | 25 372 | 7.5E-04 | −22.00 | 2.8E-07 |
| E376K | EUR | 20 401 | 2.5E-05 | −62.77 | 2.3E-02 | ||
| E445K | AFR | 4 971 | 3.7E-03 | −20.99 | 1.3E-06 | ||
| FVIII | |||||||
| rs7962217 | G2705R | VWF | ALL | 28 291 | 4.6E-02 | 5.16 | 2.5E-13 |
| EUR | 20 030 | 5.5E-02 | 4.84 | 4.0E-11 | |||
| AFR | 6 079 | 1.6E-02 | 8.58 | 7.9E-03 | |||
| ASI | 764 | 7.2E-03 | 17.63 | 3.0E-01 | |||
| HIS | 1 418 | 5.8E-02 | 10.21 | 2.7E-02 | |||
| rs41276738 (new) | R854Q | VWF | ALL | 28 291 | 4.0E-03 | −16.89 | 2.2E-13 |
| EUR | 20 030 | 5.3E-03 | −15.96 | 9.2E-12 | |||
| AFR | 6 079 | 9.9E-04 | −49.57 | 3.8E-04 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 418 | 1.1E-03 | −19.47 | 5.5E-01 | |||
| rs141041254 (new) | E2377K | STAB2 | ALL | 28 291 | 8.7E-04 | 26.81 | 2.1E-08 |
| EUR | 20 030 | 1.2E-03 | 28.06 | 7.6E-09 | |||
| AFR | 6 079 | 2.5E-04 | −11.70 | 6.6E-01 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 418 | 0 | NA | NA | |||
| rs1800291 | D1260E | F8 | ALL | 28 291 | 2.7E-01 | −1.73 | 8.2E-08 |
| EUR | 20 030 | 1.7E-01 | −2.15 | 5.0E-09 | |||
| AFR | 6 079 | 3.5E-01 | −0.54 | 4.5E-01 | |||
| ASI | 764 | 4.7E-02 | 7.29 | 1.8E-01 | |||
| HIS | 1 418 | 2.5E-01 | 0.28 | 8.9E-01 | |||
| rs142508811 (new) | D413D | KATNB1 | ALL | 28 291 | 2.7E-04 | 39.36 | 4.8E-04 |
| D410D | EUR | 20 030 | 1.8E-04 | 1.08 | 9.4E-01 | ||
| (predicted to alter splicing) | AFR | 6 079 | 6.6E-04 | 86.35 | 2.8E-07 | ||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 418 | 0 | NA | NA | |||
| vWF | |||||||
| rs141041254 (new) | E2377K | STAB2 | ALL | 23 272 | 8.2E-04 | 33.65 | 2.4E-07 |
| EUR | 18 236 | 9.9E-04 | 35.21 | 1.1E-07 | |||
| AFR | 5 036 | 2.0E-04 | −11.56 | 7.5E-01 |
| Factor and variant . | AA Change*† . | Gene . | Ancestry . | No. of participants in study . | MAF‡ . | β . | P . |
|---|---|---|---|---|---|---|---|
| Fibrinogen | |||||||
| rs201909029 (new) | K178N (K148N) | FGB | ALL | 76 316 | 7.7E-04 | −0.139 | 3.2E-13 |
| EUR | 65 733 | 8.8E-04 | −0.139 | 5.2E-13 | |||
| AFR | 8 388 | 6.0E-05 | −0.163 | 4.3E-01 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 3.5E-04 | −0.117 | 5.5E-01 | |||
| rs6054 | P265L (P235L) | FGB | ALL | 76 316 | 4.2E-03 | −0.111 | 1.8E-43 |
| EUR | 65 733 | 4.7E-03 | −0.111 | 3.7E-42 | |||
| AFR | 8 388 | 1.2E-03 | −0.104 | 2.6E-02 | |||
| ASI | 764 | 1.3E-03 | −0.130 | 3.0E-01 | |||
| HIS | 1 431 | 0 | NA | NA | |||
| rs145051028 (new) | S245F (S219F) | FGG | ALL | 76 316 | 1.6E-04 | −0.239 | 4.8E-09 |
| EUR | 65 733 | 0 | NA | NA | |||
| AFR | 8 388 | 1.5E-03 | −0.239 | 4.8E-09 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 0 | NA | NA | |||
| rs148685782 | A108G (A82G) | FGG | ALL | 76 316 | 3.3E-03 | −0.238 | 9.2E-152 |
| EUR | 65 733 | 3.8E-03 | −0.239 | 2.3E-150 | |||
| AFR | 8 388 | 4.2E-04 | −0.165 | 3.4E-02 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 3.5E-04 | −0.347 | 7.7E-02 | |||
| rs10479001 | A225V | PDLIM4 | ALL | 76 316 | 5.5E-02 | 0.013 | 1.3E-08 |
| EUR | 65 733 | 4.5E-02 | 0.018 | 4.3E-11 | |||
| AFR | 8 388 | 1.4E-01 | −0.001 | 8.3E-01 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 5.5E-02 | 0.019 | 2.3E-01 | |||
| rs1800961 | T117I | HNF4A | ALL | 76 316 | 2.7E-02 | −0.020 | 2.3E-10 |
| T139I | EUR | 65 733 | 3.0E-02 | −0.020 | 5.5E-10 | ||
| T169I | AFR | 8 388 | 5.9E-03 | 0.012 | 5.5E-01 | ||
| ASI | 764 | 1.1E-02 | −0.031 | 4.8E-01 | |||
| HIS | 1 431 | 4.2E-02 | −0.038 | 4.0E-02 | |||
| rs151272083 (new) | R865Q | KCNT1 | ALL | 76 316 | 2.2E-03 | 0.007 | 5.3E-01 |
| R877Q | EUR | 65 733 | 2.4E-03 | 0.017 | 1.3E-01 | ||
| R891Q | AFR | 8 388 | 7.2E-04 | −0.330 | 2.7E-07 | ||
| R910Q | ASI | 764 | 0 | NA | NA | ||
| HIS | 1 431 | 0 | NA | NA | |||
| rs141869748 (new) | I193T | HID1 | ALL | 76 316 | 1.6E-04 | −0.216 | 4.2E-07 |
| I421T | EUR | 65 733 | 0 | NA | NA | ||
| AFR | 8 388 | 1.3E-03 | −0.252 | 4.0E-08 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 431 | 1.1E-03 | 0.008 | 9.4E-01 | |||
| FVII | |||||||
| rs150525536 (new) | R117Q | F7 | ALL | 25 372 | 9.5E-04 | −31.44 | 1.8E-17 |
| R70Q | EUR | 20 401 | 9.8E-05 | −13.92 | 2.2E-01 | ||
| R139Q | AFR | 4 971 | 4.4E-03 | −33.56 | 9.7E-18 | ||
| rs121964926 (new) | R342Q | F7 | ALL | 25 372 | 1.2E-03 | −25.02 | 1.3E-14 |
| R295Q | EUR | 20 401 | 4.2E-04 | −0.52 | 9.3E-01 | ||
| R364Q | AFR | 4 971 | 4.4E-03 | −38.08 | 2.8E-21 | ||
| rs3093248 (new) | E423K | F7 | ALL | 25 372 | 7.5E-04 | −22.00 | 2.8E-07 |
| E376K | EUR | 20 401 | 2.5E-05 | −62.77 | 2.3E-02 | ||
| E445K | AFR | 4 971 | 3.7E-03 | −20.99 | 1.3E-06 | ||
| FVIII | |||||||
| rs7962217 | G2705R | VWF | ALL | 28 291 | 4.6E-02 | 5.16 | 2.5E-13 |
| EUR | 20 030 | 5.5E-02 | 4.84 | 4.0E-11 | |||
| AFR | 6 079 | 1.6E-02 | 8.58 | 7.9E-03 | |||
| ASI | 764 | 7.2E-03 | 17.63 | 3.0E-01 | |||
| HIS | 1 418 | 5.8E-02 | 10.21 | 2.7E-02 | |||
| rs41276738 (new) | R854Q | VWF | ALL | 28 291 | 4.0E-03 | −16.89 | 2.2E-13 |
| EUR | 20 030 | 5.3E-03 | −15.96 | 9.2E-12 | |||
| AFR | 6 079 | 9.9E-04 | −49.57 | 3.8E-04 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 418 | 1.1E-03 | −19.47 | 5.5E-01 | |||
| rs141041254 (new) | E2377K | STAB2 | ALL | 28 291 | 8.7E-04 | 26.81 | 2.1E-08 |
| EUR | 20 030 | 1.2E-03 | 28.06 | 7.6E-09 | |||
| AFR | 6 079 | 2.5E-04 | −11.70 | 6.6E-01 | |||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 418 | 0 | NA | NA | |||
| rs1800291 | D1260E | F8 | ALL | 28 291 | 2.7E-01 | −1.73 | 8.2E-08 |
| EUR | 20 030 | 1.7E-01 | −2.15 | 5.0E-09 | |||
| AFR | 6 079 | 3.5E-01 | −0.54 | 4.5E-01 | |||
| ASI | 764 | 4.7E-02 | 7.29 | 1.8E-01 | |||
| HIS | 1 418 | 2.5E-01 | 0.28 | 8.9E-01 | |||
| rs142508811 (new) | D413D | KATNB1 | ALL | 28 291 | 2.7E-04 | 39.36 | 4.8E-04 |
| D410D | EUR | 20 030 | 1.8E-04 | 1.08 | 9.4E-01 | ||
| (predicted to alter splicing) | AFR | 6 079 | 6.6E-04 | 86.35 | 2.8E-07 | ||
| ASI | 764 | 0 | NA | NA | |||
| HIS | 1 418 | 0 | NA | NA | |||
| vWF | |||||||
| rs141041254 (new) | E2377K | STAB2 | ALL | 23 272 | 8.2E-04 | 33.65 | 2.4E-07 |
| EUR | 18 236 | 9.9E-04 | 35.21 | 1.1E-07 | |||
| AFR | 5 036 | 2.0E-04 | −11.56 | 7.5E-01 |
Only SNPs that were still significant after conditional analyses are included in the table. SNPs that achieved genome-wide significance threshold (ALL, P = 2.50E-07; EUR, P = 2.88E-07; AFR, P = 3.30E-07; ASI, P = 1.70E-06; and HIS, P = 4.67E-07) are shown in bold.
ALL, all ancestries (only EUR + AFR for FVII and vWF); NA, not applicable.
AA change, amino acid change of SNP.
Amino acid position in parentheses is for the mature protein for FGB (position 30) and FGG (position 26).
MAF, minor allele frequency from CHARGE joint calling.