Table 2. Summary of functional data implicating candidate causal genes in newly identified CAD regions.
Genes in region, provides genes in the LD block containing the CAD-associated SNP. Phenotype in murine model, lists the phenotype as provided in the mouse genome informatics database, genes are listed if the phenotype affects the cardiovascular system, inflammation or liver function. eQTLs are listed where the SNP or a proxy with r2>0.9 are an eQTL for the listed gene in one of the following refs: 12, 13, 26, 43, 44, 45, 46,38,47,48,14,49 (refer to Supplementary Table 10 for an extended listing where r2>0.8 between the CAD-associated SNP and the lead eQTL). Candidate genes are based on the most likely given the information ascertained on murine phenotype, eQTL, protein expression and any literature information described in the main text. Loci are further discussed in the Supplementary Information.
| SNP | Genes in region | Phenotype in murine model | Cis-eQTLs with SNP (or proxy r2>0.9) | Proteins expressed in SMC, heart, liver, blood+ | Candidate causal gene(s) |
|---|---|---|---|---|---|
| rs1892094C>T | ATP1B1, BLZF1, CCDC181, F5, NME7, SELP, SLC19A2 | ATP1B1 (cardiovascular, homeostasis, mortality/aging, muscle) F5 (blood coagulation) SELP (cardiovascular, coagulation, inflammatory response) | NME7*, ATP1B1* | ATP1B1, NME7, SELP | ATP1B1, NME7 |
| rs6700559C>T | CAMSAP2, DDX59, KIF14 | CAMSAP2*, DDX59* | CAMSAP2, DDX59, KIF14 | CAMSAP2, DDX59 | |
| rs2820315C>T | IPO9, LMOD1, NAV1, SHISA4, TIMM17A | LMOD1, IPO9* | LMOD1 | LMOD1 | |
| rs2571445G>A | CXCR2, RUFY4, TNS1 | CXCR2 (increased IL6, abnormal interleukin level) | TNS1* | TNS1, RUFY4 | TNS1 |
| rs246600C>T | ARHGAP26, FGF1 | None | |||
| rs10237377G>T | PARP12, TBXAS1 | TBXAS1 (increased bleeding, decreased platelet aggregation) | TBXAS1* | TBXAS1 | |
| rs12801636G>A | PCNX3, POLA2, RELA, RNASEH2C, SAC3D1, SCYL1, SIPA1, SLC22A20, SLC25A45, SNX15, SNX32, SPDYC, SSSCA1, SYVN1, TIGD3, TM7SF2, TMEM262, VPS51, ZFPL1, ZNHIT2 | CAPN1 (cardiovascular system), CDCA5 (decreased mean corpuscular volume), CFL1 (cardiovascular system), EFEMP2 (cardiovascular), MUS81 (cardiovascular system), RELA (CVD others), SCYL1 (small myocardial fiber), | SIPA1* | SIPA1 | |
| rs590121G>T | GDPD5, KLHL35, SERPINH1 | SERPINH1 (hemorrhage) | SERPINH1* | SERPINH1 | SERPINH1 |
| rs2258287C>A | SPPL3, HNF1A-AS1, HNF1A, C12orf43, OASL, P2RX7, P2RX4 | HNF1A (increased cholesterol, decreased liver function) P2RX4 (abnormal vascular endothelial cell physiology, abnormal vasodilation, abnormal common carotid artery morphology) | C12orf43, SPPL3, P2RX7, P2RX4 | ||
| rs11057830G>A | SCARB1, UBC | SCARB1 (increased susceptibility to atherosclerosis, reduced heart rate, abnormal lipoprotein metabolism abnormal vascular wound healing) | None | UBC | SCARB1 |
| rs6494488A>G | ANKDD1A, CSNK1G1, DAPK2, FAM96A, KIAA0101, OAZ2, PIF1, PLEKHO2, PPIB, RBPMS2, SNX1, SNX22, TRIP4, ZNF609 | PIF1 (abnormal telomere length) | ANKDD1A*, RBPMS2*, TRIP4* | TRIP4 | TRIP4 |
| rs1050362C>A | AP1G1, ATXN1L, CALB2, CHST4, DHODH, DHX38, HP, HPR | HP (renal, development of atherosclerosis25) | DHODH*, HP*, DHX38* | HP, DHX38, DHODH | HP |
| rs17608766T>C | ARL17A, CDC27, GOSR2, MYL4, WNT9B, WNT3 | GOSR2* | GOSR2 | ||
| rs1867624T>C | DDX5, MILR1, PECAM1, POLG2, TEX2 | DDX5 (abnormal vascular development), PECAM1 (cardiovascular system, liver inflammation) | PECAM1* | PECAM1, TEX2 | PECAM1 |
| rs867186A>G | RALY, EIF2S2, ASIP, AHCY, ITCH, DYNLRB1, MAP1LC3A,PIGU, HMGB3P1, GGT7, ACSS2, NCOA6, GSS, MYH7B, TRPC4AP, EDEM2, PROCR, MMP24, EIF6 | ASIP (cardiovascular system), NCOA6 (cardiovascular system), PROCR (abnormal circulatiung C-reactive protein and fibrinogen levels; thrombosis/blood coagulation), | PROCR*, EIF6*, ITGB4BP* | EIF6, ITGB4BP | PROCR |
| rs6088590 C>T | PROCR*, GGT7*, MAP1LC3A*, ACSS2*, TRPC4AP* | GGT7 |
indicates that the eQTL is identified in one of blood (including peripheral blood mononuclear cells) heart, aorta/coronary artery or live. Note the PCNX3 region also encompasses AP5B1, ARL2, CAPN1, CDC42EP2, CDCA5, CFL1, CTSW, DPF2, EFEMP2, EHBP1L1, FAM89B, FAU, FRMD8, KAT5, KCNK7, LTBP3, MAP3K11, MRPL49, MUS81, NAALADL1, OVOL1. The DHX38 region also encompasses, IST1, MARVELD3, PHLPP2, PKD1L3, PMFBP1, TAT, TXNL4B, ZFHX3, ZNF19, ZNF23, ZNF821. The PROCR region also includes: FAM83C, UQCC1, GDF5, SPAG4, CEP250, C20orf173, ERGIC3, FER1L4, CPNE1, RBM12, NFS1, ROMO1, RBM39, SCAND1, CNBD2, EPB41L1, LINC00657, AAR2, DLGAP4