Table 2.
Top cis-eSNP associations after adjustment for previously reported GWAS SNPs
| Gene | Clinical phenotype | C hr | Top 1, cis-eSNP | P, cis-eSNP | #cis- eSNP P < 5 × 10−8 | Clinical SNP used for adjustment (clinSNP) | R2 (eSNP versus. clinSNP) | GWAS clinical traits | P, clinSNP in GWAS | P, cis-eSNP after adjust for clinSNP |
|---|---|---|---|---|---|---|---|---|---|---|
| ABO | Hemostatic, CAD, others | 9 | Rs8176731 | 1.12 × 10−91 | 120 | rs687621 | 0.04 | vWF | <5.00 × 10−324 | 6.61 × 10−87 |
| rs687289 | 0.04 | FVIII | <5.00 × 10−324 | 6.35 × 10−87 | ||||||
| rs579459 | 0.10 | CAD | 4.00 × 10−14 | 8.84 × 10−81 | ||||||
| FADS2 | Lipid, CAD | 11 | Rs968567a | 5.72 × 10−73 | 64 | rs174546 | 0.47 | TG, HDL, TC,LDL | 5.40 × 10−24 | 6.71 × 10−22 |
| rs174626b | 0.32 | CAD | 5.30 × 10−3 | 1.33 × 10−54 | ||||||
| LPL | Lipid, CAD | 8 | rs6993414 | 1.21 × 10−52 | 127 | rs12678919c | 1.00 | TG,HDL | 1.50 × 10−115 | 3.00 × 10−3 |
| rs3779788 | 0.34 | CAD | 2.40 × 10−7 | 1.74 × 10−27 | ||||||
| APOC2 | Lipid, CAD | 19 | rs2288912 | 1.98 × 10−36 | 32 | rs4420638 | 0.00 | LDL,TC | 8.72 × 10−147 | 3.20 × 10−36 |
| rs4420638d | 0.00 | CAD | 2.14 × 10−4 | 3.20 × 10−36 | ||||||
| FNTB | RBC traits | 14 | rs7148144 | 1.90 × 10−22 | 7 | rs4466998 | 0.06 | MCV | 4.90 × 10−8 | 1.14 × 10−20 |
| CDKN2B | CAD, CAC | 9 | rs598664 | 1.86 × 10−13 | 18 | rs4977574 | 0.08 | CAD, CAC | 1.35 × 10−22 | 9.49 × 10−14 |
| FAM117B | CAD | 2 | rs1971739 | 2.93 × 10−11 | 9 | rs6705330 | 0.27 | CAD | 8.98 × 10−11 | 4.17 × 10−7 |
| C6orf184e | CAD | 6 | rs7773213 | 7.07 × 10−11 | 17 | rs9374080 | 0.68 | MCV | 3.70 × 10−8 | 3.20 × 10−2 |
| CDKN2BAS-S* | CAD, CAC | 9 | rs1360590 | 4.58 × 10−10 | 18 | rs4977574 | 0.43 | CAD, CAC | 1.35 × 10−22 | 1.85 × 10−6 |
| SCARA5 | Hemostatic | 8 | rs7003622 | 3.70 × 10−8 | 1 | rs2726953 | 0.01 | vWF | 1.30 × 10−16 | 2.80 × 10−8 |
| rs9644133 | 0.00 | FVIII | 4.40 × 10−15 | 2.71 × 10−8 |
ars968567 was also reported to be significantly associated with the expression level of FADS2 in other blood-related eQTL studies (Supplementary Material, Table S3a)
brs174626 is not found in GWAS catalog, and FADS2 is not found to be associated with CAD in GWAS catalog.
crs12678919, a lead SNP in TG and HDL GWAS, is also reported to be significantly associated with the expression level of LPL in lymphocytes (Supplementary Material, Table S3a)
drs4420638 was associated with C-reactive protein (P = 9 × 10−139) and LDL cholesterol (P = 2 × 10−40) in GWAS catalog (APOC2 is not found to be associated with CAD in GWAS catalog).
eC6orf184 is an alias of gene CCDC162P. CDKN2BAS-S is an alias for a short transcript isoform of ANRIL.
All previously reported GWAS SNPs reach genome-wide significant (P < 5 × 10−8) except 3 SNPs associated with CAD (12): rs174626 (P = 5.30 × 10−3), rs3779788 (P = 2.40 × 10−7), and rs4420638 (P = 2.14 × 10−4).
Chr, chromosome; SNP, single-nucleotide polymorphism; clinSNP, SNP from clinical genome-wide association study used for adjustment in conditional analyses; GWAS, genome-wide association study; CAD, clinically apparent coronary artery disease; RBC, red blood cell; CAC, coronary artery calcium.