Independent genome-wide significant loci associated with VTE from transancestry meta-analyses
| Chr:Position . | Variant identifier: effective/reference allele (amino acid substitution) . | MAF: EA . | MAF: AA . | Transancestry P value . | Transancestry OR (95% CI) . | Locus (location) . | Status . |
|---|---|---|---|---|---|---|---|
| 1:169519049 | rs6025: T/C (Arg>Gln) | 0.03 | NA | 1.4E-188 | 2.39 (2.25-2.53) | F5 (exon) | Known |
| 1:169511755 | rs4524: C/T (Lys>Arg) | 0.26 | 0.19 | 3.1E-29 | 0.88 (0.86-0.90) | F5 (exon) | Known |
| 1:207282149 | rs2842700: A/C | 0.06 | 0.28 | 3.1E-10 | 1.14 (1.09-1.18) | C4BPA (intron) | New variant |
| 1:230986407 | rs145470028: T/G | 0.02 | NA | 3.0E-08 | 0.78 (0.72-0.85) | C1orf198 (intron) | New locus: not replicated |
| 2:68619981 | rs1867312: C/A | 0.43 | 0.45 | 2.5E-10 | 1.06 (1.04-1.09) | PLEK (intron) | New locus: replicated |
| 4:155525695 | rs2066864: A/G | 0.24 | 0.41 | 2.0E-59 | 1.20 (1.17-1.22) | FGG (intron) | Known |
| 4:187207381 | rs2289252: T/C | 0.40 | 0.29 | 3.0E-65 | 1.19 (1.16-1.21) | F11 (intron) | Known |
| 4:187192481 | rs2036914: T/C | 0.47 | 0.35 | 1.6E-54 | 0.86 (0.84-0.87) | F11 (intron) | Known |
| 4:187204937 | rs4253421: A/G | 0.12 | 0.04 | 8.1E-41 | 0.80 (0.78-0.83) | F11 (intron) | New variant |
| 5:38707871 | rs4869589: T/G | 0.26 | 0.27 | 7.6E-10 | 1.07 (1.05-1.10) | OSMR-AS1 (intron) | New locus: replicated |
| 6:147701133 | rs9373523: T/G | 0.42 | 0.28 | 5.4E-09 | 0.94 (0.93-0.96) | STXBP5 (intron) | Known |
| 8:27898452 | rs12675621: G/A | 0.29 | 0.35 | 2.4E-09 | 1.07 (1.04-1.09) | NUGGC (intron), SCARA5 (upstream) | New locus: not replicated |
| 8:106590705 | rs4541868: A/C | 0.25 | 0.39 | 7.1E-14 | 0.92 (0.90-0.94) | ZFPM2 (intron) | Known |
| 9:136131188 | rs8176749: T/C (Leu>Leu) | 0.08 | 0.16 | 2.3E-30 | 1.23 (1.19-1.28) | ABO (exon) | Known |
| 9:136137106 | rs687289: A/G | 0.35 | 0.41 | 1.3E-174 | 1.34 (1.31-1.36) | ABO (intron) | Known |
| 9:136141870 | rs2519093: T/C | 0.21 | 0.11 | 3.8E-169 | 1.40 (1.37-1.43) | ABO (intron) | Known |
| 9:136154168 | rs579459: C/T | 0.23 | 0.14 | 3.9E-145 | 1.36 (1.33-1.39) | ABO (intron) | Known |
| 10:71245276 | rs78707713: C/T | 0.12 | 0.02 | 2.6E-30 | 0.83 (0.81-0.86) | TSPAN15 (intron) | Known |
| 10:121010256 | rs10886430: G/A | 0.13 | 0.03 | 2.2E-12 | 1.12 (1.09-1.16) | GRK5 (intron) | New locus: replicated |
| 11:46933311 | rs191945075: A/G | 0.01 | NA | 9.5E-32 | 1.86 (1.68-2.07) | LRP4 (intron), F2 (downstream) | Known |
| 11:46760756 | rs3136516: G/A | 0.47 | 0.12 | 1.0E-15 | 1.08 (1.06-1.11) | F2 (intron) | Known |
| 12:6153738 | rs1558519: G/A | 0.35 | 0.44 | 3.7E-13 | 1.08 (1.06-1.10) | VWF (intron) | Known |
| 12:6128443 | rs216311: T/C (Thr>Ala) | 0.39 | 0.12 | 1.8E-02* | 0.98 (0.96-1.00) | VWF (exon) | New variant |
| 12:123667354 | rs2851436: G/T | 0.21 | 0.27 | 3.9E-08 | 0.94 (0.91-0.96) | MPHOSPH9 (intronic) | New locus: replicated |
| 14:58844526 | rs11158204: T/C | 0.25 | 0.25 | 1.5E-08 | 0.94 (0.92-0.96) | Intragenic, ARID4A (downstream) | New locus: not replicated |
| 16:81870969 | rs12445050: T/C | 0.14 | 0.03 | 6.7E-13 | 1.11 (1.08-1.14) | PLCG2 (intron) | New locus: replicated |
| 17:1966457 | rs1048483: T/C | 0.49 | 0.30 | 3.4E-09 | 1.06 (1.04-1.08) | SMG6 (intron) | New locus: replicated |
| 17:7207887 | rs12450494: A/T | 0.47 | 0.18 | 1.0E-07† | 1.06 (1.03-1.08) | Intergenic, EIF5A (upstream) | New locus: not replicated |
| 19:10740871 | rs4548995: G/C | 0.22 | 0.16 | 3.7E-19 | 0.90 (0.87-0.92) | SCL44A2 (intron) | Known |
| 19:13258290 | rs7508633: G/A | 0.45 | 0.32 | 2.0E-09 | 1.06 (1.04-1.09) | STX10 (intron) | New locus: not replicated |
| 19:55511873 | rs1671135: G/C | 0.21 | 0.23 | 2.9E-09 | 0.93 (0.90-0.95) | NLRP2 (intron), GP6 (downstream) | Known |
| 20:33745676 | rs6088735: T/C | 0.23 | 0.32 | 3.0E-10 | 1.08 (1.05-1.10) | PROCR (intron) | Known |
| 20:33764554 | rs867186: G/A (Ser>Gly) | 0.10 | 0.09 | 6.8E-09 | 1.11 (1.07-1.14) | PROCR (exon) | Known |
| X:154424170 | rs143478537: G/C | 0.14 | NA | 3.1E-08‡ | 1.08 (1.05-1.11) | F8 (upstream) | Known |
| Chr:Position . | Variant identifier: effective/reference allele (amino acid substitution) . | MAF: EA . | MAF: AA . | Transancestry P value . | Transancestry OR (95% CI) . | Locus (location) . | Status . |
|---|---|---|---|---|---|---|---|
| 1:169519049 | rs6025: T/C (Arg>Gln) | 0.03 | NA | 1.4E-188 | 2.39 (2.25-2.53) | F5 (exon) | Known |
| 1:169511755 | rs4524: C/T (Lys>Arg) | 0.26 | 0.19 | 3.1E-29 | 0.88 (0.86-0.90) | F5 (exon) | Known |
| 1:207282149 | rs2842700: A/C | 0.06 | 0.28 | 3.1E-10 | 1.14 (1.09-1.18) | C4BPA (intron) | New variant |
| 1:230986407 | rs145470028: T/G | 0.02 | NA | 3.0E-08 | 0.78 (0.72-0.85) | C1orf198 (intron) | New locus: not replicated |
| 2:68619981 | rs1867312: C/A | 0.43 | 0.45 | 2.5E-10 | 1.06 (1.04-1.09) | PLEK (intron) | New locus: replicated |
| 4:155525695 | rs2066864: A/G | 0.24 | 0.41 | 2.0E-59 | 1.20 (1.17-1.22) | FGG (intron) | Known |
| 4:187207381 | rs2289252: T/C | 0.40 | 0.29 | 3.0E-65 | 1.19 (1.16-1.21) | F11 (intron) | Known |
| 4:187192481 | rs2036914: T/C | 0.47 | 0.35 | 1.6E-54 | 0.86 (0.84-0.87) | F11 (intron) | Known |
| 4:187204937 | rs4253421: A/G | 0.12 | 0.04 | 8.1E-41 | 0.80 (0.78-0.83) | F11 (intron) | New variant |
| 5:38707871 | rs4869589: T/G | 0.26 | 0.27 | 7.6E-10 | 1.07 (1.05-1.10) | OSMR-AS1 (intron) | New locus: replicated |
| 6:147701133 | rs9373523: T/G | 0.42 | 0.28 | 5.4E-09 | 0.94 (0.93-0.96) | STXBP5 (intron) | Known |
| 8:27898452 | rs12675621: G/A | 0.29 | 0.35 | 2.4E-09 | 1.07 (1.04-1.09) | NUGGC (intron), SCARA5 (upstream) | New locus: not replicated |
| 8:106590705 | rs4541868: A/C | 0.25 | 0.39 | 7.1E-14 | 0.92 (0.90-0.94) | ZFPM2 (intron) | Known |
| 9:136131188 | rs8176749: T/C (Leu>Leu) | 0.08 | 0.16 | 2.3E-30 | 1.23 (1.19-1.28) | ABO (exon) | Known |
| 9:136137106 | rs687289: A/G | 0.35 | 0.41 | 1.3E-174 | 1.34 (1.31-1.36) | ABO (intron) | Known |
| 9:136141870 | rs2519093: T/C | 0.21 | 0.11 | 3.8E-169 | 1.40 (1.37-1.43) | ABO (intron) | Known |
| 9:136154168 | rs579459: C/T | 0.23 | 0.14 | 3.9E-145 | 1.36 (1.33-1.39) | ABO (intron) | Known |
| 10:71245276 | rs78707713: C/T | 0.12 | 0.02 | 2.6E-30 | 0.83 (0.81-0.86) | TSPAN15 (intron) | Known |
| 10:121010256 | rs10886430: G/A | 0.13 | 0.03 | 2.2E-12 | 1.12 (1.09-1.16) | GRK5 (intron) | New locus: replicated |
| 11:46933311 | rs191945075: A/G | 0.01 | NA | 9.5E-32 | 1.86 (1.68-2.07) | LRP4 (intron), F2 (downstream) | Known |
| 11:46760756 | rs3136516: G/A | 0.47 | 0.12 | 1.0E-15 | 1.08 (1.06-1.11) | F2 (intron) | Known |
| 12:6153738 | rs1558519: G/A | 0.35 | 0.44 | 3.7E-13 | 1.08 (1.06-1.10) | VWF (intron) | Known |
| 12:6128443 | rs216311: T/C (Thr>Ala) | 0.39 | 0.12 | 1.8E-02* | 0.98 (0.96-1.00) | VWF (exon) | New variant |
| 12:123667354 | rs2851436: G/T | 0.21 | 0.27 | 3.9E-08 | 0.94 (0.91-0.96) | MPHOSPH9 (intronic) | New locus: replicated |
| 14:58844526 | rs11158204: T/C | 0.25 | 0.25 | 1.5E-08 | 0.94 (0.92-0.96) | Intragenic, ARID4A (downstream) | New locus: not replicated |
| 16:81870969 | rs12445050: T/C | 0.14 | 0.03 | 6.7E-13 | 1.11 (1.08-1.14) | PLCG2 (intron) | New locus: replicated |
| 17:1966457 | rs1048483: T/C | 0.49 | 0.30 | 3.4E-09 | 1.06 (1.04-1.08) | SMG6 (intron) | New locus: replicated |
| 17:7207887 | rs12450494: A/T | 0.47 | 0.18 | 1.0E-07† | 1.06 (1.03-1.08) | Intergenic, EIF5A (upstream) | New locus: not replicated |
| 19:10740871 | rs4548995: G/C | 0.22 | 0.16 | 3.7E-19 | 0.90 (0.87-0.92) | SCL44A2 (intron) | Known |
| 19:13258290 | rs7508633: G/A | 0.45 | 0.32 | 2.0E-09 | 1.06 (1.04-1.09) | STX10 (intron) | New locus: not replicated |
| 19:55511873 | rs1671135: G/C | 0.21 | 0.23 | 2.9E-09 | 0.93 (0.90-0.95) | NLRP2 (intron), GP6 (downstream) | Known |
| 20:33745676 | rs6088735: T/C | 0.23 | 0.32 | 3.0E-10 | 1.08 (1.05-1.10) | PROCR (intron) | Known |
| 20:33764554 | rs867186: G/A (Ser>Gly) | 0.10 | 0.09 | 6.8E-09 | 1.11 (1.07-1.14) | PROCR (exon) | Known |
| X:154424170 | rs143478537: G/C | 0.14 | NA | 3.1E-08‡ | 1.08 (1.05-1.11) | F8 (upstream) | Known |
Bold text indicates novel associations.
CI, confidence interval; OR, odds ratio.
For rs216311, the EA meta-analysis P value was 5.3E-09 (OR 0.94) after conditioning on rs1558519, the strongest signal in VWF.
For rs12450494, the EA-only P value was 2.5E-08 (OR 1.06), which qualified it for genome-wide significance.
For rs143478537, meta-analysis was by done using a sample-size weighted model in EA only so no odds ratio and MAF in AA was estimated.