Table II. Top Significant SNP Associations for FVIII:C and VWF:Ag at P value <2.0 × 10−6 in EAs and AAs of CARe (Ordered by Chromosome).
| Trait | Region | Top SNP | Position | A1/A2 | AFA1 | Gene (var) | Beta/SE, % | P value | Var% | Imput | Note |
|---|---|---|---|---|---|---|---|---|---|---|---|
| EA | |||||||||||
| FVIII | 3q27 | rs698078a | 187941921 | A/G | 0.59 | KNG1 (intr) | 1.99/0.38 | 4.26 × 10−7 | 0.33 | 0.95–1.00 | New |
| FVIII | 3q27 | rs710446a | 187942621 | T/C | 0.59 | KNG1 (cns) | 1.97/0.39 | 5.10 × 10−7 | 0.33 | – | New |
| FVIII | 9q34.1-.2 | rs529565 | 135139321 | T/C | 0.65 | ABO (intr) | 17.03/0.37 | <1.0 × 10−199 | 11.57 | 0.98–1.05 | Repl |
| FVIII | 12p13.3 | rs1063856 | 6023795 | T/C | 0.64 | VWF (cns) | 2.68/0.40 | 5.84 × 10−12 | 0.32 | – | Repl |
| FVIII | 12p13.3 | rs7962217 | 5931820 | C/T | 0.94 | VWF (cns) | 4.84/0.83 | 6.30 × 10−9 | 0.21 | – | New |
| FVIII | 12p13.3 | rs216321 | 6014245 | C/T | 0.91 | VWF (cns) | −3.99/0.67 | 4.70 × 10−10 | 0.19 | – | New |
| FVIII | Xq28 | rs12557310b | 154388892 | C/T | 0.72 | TMLHE (intr) | −2.94/0.48 | 8.02 × 10−10 | 1.86 | – | New |
| FVIII | Xq28 | rs2096362b | 153885468 | G/A | 0.74 | F8 (intr) | −2.82/0.49 | 1.88 × 10−9 | 0.13 | – | Repl |
| VWF | 9q34.1-.2 | rs529565 | 135139321 | T/C | 0.66 | ABO (intr) | 22.18/0.50 | <1.0 × 10−199 | 13.93 | 0.98–1.00 | Repl |
| VWF | 12p13.3 | rs1063856 | 6023795 | T/C | 0.64 | VWF (cns) | 4.83/0.54 | 1.06 × 10−19 | 0.88 | – | Repl |
| VWF | 12p13.3 | rs216321 | 6014245 | C/T | 0.91 | VWF (cns) | −7.24/0.92 | 1.71 × 10−17 | 0.48 | – | Repl |
| AA | |||||||||||
| FVIII | 9q34.1-.2 | rs8176693 | 135127478 | C/T | 0.90 | ABO (intr) | 37.24/1.65 | 2.51 × 10−114 | 8.62 | 0.66–0.78 | Repl |
| FVIII | 10q22 | rs2236568 | 82025903 | A/C | 0.76 | MAT1A (intr) | 5.28/1.06 | 1.69 × 10−6 | 0.69 | – | New |
| FVIII | 12p13.3 | rs2229446 | 5973333 | C/T | 0.81 | VWF (cns) | −9.47/1.13 | 1.95 × 10−20 | 1.16 | – | Repl |
| FVIII | 12p13.3 | rs1800380 | 6008856 | C/T | 0.70 | VWF (cs) | 5.72/0.95 | 5.62 × 10−11 | 0.35 | 0.92–1.00 | New |
| FVIII | 12p13.3 | rs4764482c | 6039994 | T/C | 0.80 | VWF (intr) | −5.74/1.10 | 8.12 × 10−8 | 0.74 | – | Repl |
| VWF | 9q34.1-.2 | rs8176693 | 135127478 | C/T | 0.90 | ABO (intr) | 48.62/2.37 | 1.66 × 10−89 | 10.18 | 0.65–0.74 | Repl |
| VWF | 12p13.3 | rs2229446 | 5973333 | C/T | 0.81 | VWF (cns) | −12.67/1.68 | 1.13 × 10−16 | 1.75 | – | Repl |
| VWF | 12p13.3 | rs1063856c | 6023795 | C/T | 0.59 | VWF (cns) | −8.69/1.32 | 1.72 × 10−10 | 1.21 | – | Repl |
All data presented are independent associations except those labeled with a, b, and c, A1 = allele 1 (major allele), A2 = allele 2 (minor allele), AFA1 = average allele frequency for A1 allele in the meta-analysis, var = variant class (intr = intron, cns = coding-nonsynonymous or missense, cs = coding-synonymous), Beta = change in trait level per 1 allele increase in the minor allele based on untransformed measurements, SE = standard error, Var% = variance % explained by the SNP based on the ARIC data; imput = ratio of observed to expected variance as a measure of imputation quality (range presented, “- ” for genotyped SNPs), Repl = replication.
r2 = 1.0 in the HapMap CEU sample.
r2 = 0.08 in the HapMap CEU sample.
r2 = 0.16 in the HapMap African and African American samples.