Table 1 Genes in 51 CAD-associated loci (±250 kb around the lead SNP) proposed to be causal according to different lines of evidence.
Lead SNP¥ | Chr: position* | Nearest† known gene | Genes prioritized by SMR/HEIDI‡ | Candidate genes from literature** | Genes prioritized previously based on bioinformatics approaches46,47,48 and found in gene-based association analysis49 | Conclusion | |
|---|---|---|---|---|---|---|---|
1 | rs17114036 | 1: 56 962 821 | PLPP3 (PAP2B, PPAP2B) | — | ▪ PLPP3 (PAP2B, PPAP2B) | ▪ Lempiäinen et al.47, score range 2-54 PLPP3 (PAP2B) (total score = 10) ▪ Svishcheva et al.49 PLPP3 (PAP2B) (two datasets) | PLPP3 (PAP2B) is the causal gene. |
2 | rs602633 | 1: 109 821 511 | PSRC1 | ▪ PSRC1 ← ▪ CELSR2 ← ▪ PSMA5 ← | ▪ SORT1 ▪ PSRC1 ▪ CELSR2 | Brænne et al.46, score range 1-11 ▪ CELSR2 (total score = 5) ← ▪ SORT1 (total score = 4) ← ▪ PSRC1 (total score = 4) ← ▪ MYBPHL (total score = 2) Lempiäinen et al.47, score range 2-54 ▪ CELSR2 (total score = 10) ← van der Harst et al.48 ▪ SORT1¶ ← ▪ CELSR2 ← ▪ PSRC1 ← ▪ SARS ← ▪ ATXN7L2 ← Svishcheva et al.49 ▪ CELSR2 (two datasets) | SORT1 is the causal gene. PSRC1 and CELSR2 might also be involved. |
3 | rs4129267 | 1: 154 426 264 | IL6R | ▪ IL6R ←, ← ← | ▪ IL6R | Brænne et al.46, score range 1-11 ▪ IL6R (total score = 5) ← ▪ UBAP2L (total score = 2) ← ▪ ATP8B2 (total score = 2) ← ▪ CHTOP (total score = 1) ← Lempiäinen et al.47, score range 2-54 ▪ IL6R (total score = 10) ←, ← ← | IL6R is the causal gene. |
4 | rs10919065 | 1: 169 093 557 | ATP1B1 | ▪ ATP1B1 ← ← ▪ NME7 ←, ← ← | ▪ ATP1B1 | Brænne et al.46, score range 1-11 ▪ ATP1B1 (total score = 4) ← ▪ NME7 (total score = 2) ← ▪ CCDC181 (total score = 1) ← | ATP1B1 is the most likely causal gene. |
5 | rs6700559 | 1: 200 646 073 | DDX59-AS1 | ▪ DDX59-AS1 (RP11-92G12.3) ← ▪ DDX59 ← ▪ CAMSAP2 (CAMSAP1L1) ← | — | Brænne et al.46, score range 1-11 ▪ KIF14 (total score = 4) ← ▪ CAMSAP2 (total score = 2) ← ▪ DDX59 (total score = 2) ← van der Harst et al.48 ▪ CAMSAP2¶ ← ▪ DDX59 ← | Evidence is inconsistent. |
6 | rs2820315 | 1: 201 872 264 | LMOD1 | ▪ IPO9 ← ▪ LMOD1 ← | ▪ LMOD1 | Brænne et al.46, score range 1-11 ▪ IPO9 (total score = 4) ← ▪ LMOD1 (total score = 2) ← ▪ SHISA4 (total score = 1) ← Lempiäinen et al.47, score range 2-54 ▪ IPO9 (total score = 10) ← | Evidence is inconsistent. LMOD1 and IPO9 can be involved. |
7 | rs16986953 | 2: 19 942 473 | LINC00954 | — | — | — | No evidence. |
8 | rs515135 | 2: 21 286 057 | APOB | — | ▪ APOB | Lempiäinen et al.47, score range 2-54 ▪ APOB (total score = 32) Svishcheva et al.49 ▪ APOB (one dataset) | APOB is the causal gene. |
9 | rs6544713 | 2: 44 073 881 | ABCG8 | — | ▪ ABCG8 ▪ ABCG5 | Lempiäinen et al.47, score range 2-54 ▪ ABCG8 (total score = 34) Svishcheva et al.49 ▪ ABCG8 (two datasets) | ABCG8/ABCG5 are the causal genes. |
10 | rs1561198 | 2: 85 809 989 | VAMP8 | ▪ GGCX ← ▪ VAMP5 ← ▪ VAMP8 ← ▪ USP39 ← ▪ GNLY ← | ▪ GGCX ▪ VAMP8 | Brænne et al.46, score range 1-11 ▪ GGCX (total score = 5) ← ▪ VAMP5 (total score = 5) ← ▪ VAMP8 (total score = 5) ← Lempiäinen et al.47, score range 2-54 ▪ VAMP8 (total score = 42) ← Svishcheva et al.49 ▪ MAT2A (one dataset) ▪ GGCX (one dataset) ▪ VAMP5 (one dataset) | Evidence is inconsistent. |
11 | rs2252641 | 2: 145 801 461 | TEX41 | — | ▪ ZEB2 | Lempiäinen et al.47, score range 2-54 ▪ TEX41 (total score = 2) | Evidence is inconsistent. |
12 | rs2351524 | 2: 203 880 992 | NBEAL1 | ▪ ICA1L ← ▪ CARF ← ▪ NBEAL1 ← ▪ FAM117B ← | ▪ WDR12 | Brænne et al.46, score range 1-11 ▪ NBEAL1 (total score = 4) ← ▪ WDR12 (total score = 4) ← ▪ CARF (total score = 3) ← ▪ ALS2CR8 (total score = 2) ← ▪ ICA1L (total score = 1) ← Lempiäinen et al.47, score range 2-54 ▪ ICA1L (total score = 10) ← Svishcheva et al.49 ▪ NBEAL1 (two datasets) ▪ WDR12 (two datasets) | Evidence is inconsistent. |
13 | rs2306374 | 3: 138 119 952 | MRAS | ▪ MRAS ← ▪ NME9 ← ▪ ESYT3 ← | ▪ MRAS | Brænne et al.46, score range 1-11 ▪ MRAS (total score = 5) ← ▪ CEP70 (total score = 2) ← Lempiäinen et al.47, score range 2-54 ▪ MRAS (total score = 34) ← Svishcheva et al.49 ▪ MRAS (one dataset) | MRAS is the causal gene. |
14 | rs1429141 | 4: 148 288 067 | MIR548G | — | ▪ EDNRA (ETA) | Lempiäinen et al.47, score range 2-54 ▪ EDNRA (ETA) (total score = 34) Svishcheva et al.49 ▪ EDNRA (ETA) (one dataset) | EDNRA is the causal gene. |
15 | rs7692387 | 4: 156 635 309 | GUCY1A1 | ▪ GUCY1A3 ← | ▪ GUCY1A3 | Lempiäinen et al.47, score range 2-54 ▪ GUCY1A3 (total score = 42) ← | GUCY1A3 is the causal gene. |
16 | rs273909 | 5: 131 667 353 | SLC22A4 MIR3936HG | — | — | Lempiäinen et al.47, score range 2-54 ▪ SLC22A5 (total score = 10) | Insufficient evidence. |
17 | rs246600 | 5: 142 516 897 | ARHGAP26 | — | — | van der Harst et al.48 ▪ HMHB1 | Insufficient evidence. |
18 | rs7751826 | 6: 12 900 977 | PHACTR1 | ▪ RP1-257A7.5 ← ▪ RP1-257A7.4 ← ▪ PHACTR1 ← | ▪ PHACTR1 | Lempiäinen et al.47, score range 2-54 ▪ PHACTR1 (total score = 2) ←, ← ← van der Harst et al.48 ▪ EDN1¶ ← ← ▪ TBC1D7 ← ← ▪ PHACTR1 ← ← ▪ GFOD1 ← ← Svishcheva et al.49 ▪ PHACTR1 (two datasets) | PHACTR1 is the causal gene. |
19 | rs10947789 | 6: 39 174 922 | KCNK5 | — | — | Lempiäinen et al.47, score range 2-54 ▪ KCNK5 (total score = 2) | Insufficient evidence. |
20 | rs2327429 | 6: 134 209 837 | TARID | ▪ TCF21 ← ▪ RP3-323P13.2 ← ▪ RP1-283K11.3 ← | ▪ TCF21 | Lempiäinen et al.47, score range 2-54 ▪ TCF21 (total score = 10) ← | TCF21 is the causal gene. RP3-323P13.2 might also be involved. |
21 | rs3103349# | 6: 160 740 721 | SLC22A3 | ▪ LPA | ▪ LPA (APOA) | Brænne et al.46, score range 1-11 ▪ SLC22A3 (total score = 5) ← ← ▪ AL591069.5 (total score = 1) ← ← Lempiäinen et al.47, score range 2-54 ▪ LPA (total score = 54) ▪ LPAL2 pseudogene (total score = 10) ← ← ▪ IGF2R (total score = 2) ▪ SLC22A2 (total score = 2) ▪ SLC22A3 (total score = 2) Svishcheva et al.49 ▪ LPA (two datasets) ▪ SLC22A1 (two datasets) ▪ SLC22A2 (two datasets) ▪ SLC22A3 (two datasets) ▪ IGF2R (one dataset) | LPA is the causal gene. SLC22A3, SLC22A2, SLC22A1 might also be involved. |
22 | rs10455872# | 6: 161 010 118 | LPA | ▪ LPA ← ← | ▪ LPA (APOA) | Brænne et al.46, score range 1-11 ▪ PLG (total score = 6) ← ▪ SLC22A3 (total score = 5) ← ← ▪ LPAL2 pseudogene (total score = 4) ← ▪ AL591069.5 (total score = 1) ← ← Lempiäinen et al.47, score range 2-54 ▪ LPA (total score = 54) ▪ PLG (total score = 46) ← ▪ LPAL2 pseudogene (total score = 10) ← ← ▪ SLC22A3 (total score = 2) Svishcheva et al.49 ▪ SLC22A3 (two datasets) ▪ LPA (two datasets) ▪ PLG (two datasets) | LPA is the causal gene. PLG and SLC22A3 might also be involved. |
23 | rs11556924 | 7: 129 663 496 | ZC3HC1(NIPA) | ▪ KLHDC10 ← | ▪ KLHDC10 ▪ ZC3HC1 (NIPA) | Brænne et al.46, score range 1-11 ▪ ZC3HC1 (NIPA) (total score = 4) ← Lempiäinen et al.47, score range 2-54 ▪ ZC3HC1 (NIPA) (total score = 22) ← van der Harst et al.48 ▪ ZC3HC1¶ ← ▪ NRF1 ← ▪ KLF14 ← Svishcheva et al.49 ▪ ZC3HC1 (one dataset) | ZC3HC1 (NIPA) is the most likely causal gene. KLHDC10 might also be involved. |
24 | rs10237377 | 7: 139 757 136 | PARP12 | — | ▪ TBXAS1 | Brænne et al.46, score range 1-11 ▪ TBXAS1 (total score = 5) Lempiäinen et al.47, score range 2-54 ▪ PARP12 (total score = 10) ← ▪ TBXAS1 (total score = 10) ← | TBXAS1 is the most likely causal gene. |
25 | rs11204085 | 8: 19 940 796 | SLC18A1 | ▪ LPL | ▪ LPL | Brænne et al.46, score range 1-11 ▪ LPL (total score = 8) ← Lempiäinen et al.47, score range 2-54 ▪ LPL (total score = 42) ← Svishcheva et al.49 ▪ LPL (one dataset) | LPL is the causal gene. |
26 | rs2954032 | 8: 126 493 392 | TRIB1 | — | ▪ TRIB1 | — | TRIB1 is the causal gene. |
27 | rs3218020 | 9: 21 997 872 | CDKN2B-AS1 (ANRIL) | — | ▪ CDKN2B-AS1 (ANRIL) | Brænne et al.46, score range 1-11 ▪ CDKN2B (total score = 8) ←, ← ← ▪ CDKN2A (total score = 5) ← Lempiäinen et al.47, score range 2-54 ▪ CDKN2B (total score = 9) ← ▪ CDKN2B-AS1 (total score = 2) ← ← van der Harst et al.48 ▪ CDKN2B¶ ← ← ← ▪ MTAP← ← ← Svishcheva et al.49 ▪ CDKN2B (two datasets) ▪ CDKN2A (two datasets) ▪ MTAP (one dataset) | CDKN2B-AS1 is the causal gene, which regulates CDKN2B and CDKN2A expression. |
28 | rs579459 | 9: 136 154 168 | ABO | ▪ SURF1 ← ▪ ABO ← | ▪ ABO ▪ ADAMTS13 | Lempiäinen et al.47, score range 2-54 ▪ DDX31 (total score = 8) ← ▪ SURF1 (total score = 8) ← ▪ SURF6 (total score = 8) ← Svishcheva et al.49 ▪ ABO (one dataset) ▪ ADAMTS13 (one dataset) | Evidence is inconsistent. |
29 | rs2505083 | 10: 30 335 122 | JCAD (KIAA1462) | ▪ JCAD (KIAA1462) ← | ▪ JCAD (KIAA1462) | Brænne et al.46, score range 1-11 ▪ JCAD (KIAA1462) (total score = 6) ← Lempiäinen et al.47, score range 2-54 ▪ JCAD (KIAA1462) (total score = 6) ← Svishcheva et al.49 ▪ JCAD (KIAA1462) (one dataset) | JCAD is the causal gene. |
30 | rs10793513 | 10: 44 494 546 | LINC00841 | — | — | — | No evidence. |
31 | rs523297 | 10: 44 756 557 | CXCL12 | — | ▪ CXCL12 | — | CXCL12 is the causal gene. |
32 | rs2246833 | 10: 91 005 854 | LIPA | ▪ LIPA ← ▪ IFIT1 ← ▪ IFIT5 ← | ▪ LIPA | Brænne et al.46, score range 1-11 ▪ LIPA (total score = 9) ← Lempiäinen et al.47, score range 2-54 ▪ LIPA (total score = 46) ← Svishcheva et al.49 ▪ LIPA (one dataset) | LIPA is the causal gene. |
33 | rs11191447 | 10: 104 652 323 | BORCS7-ASMT AS3MT | ▪ TMEM180 (MFSD13A) ← ▪ ARL3 ← ▪ NT5C2 ← ▪ MARCKSL1P1 pseudogene ← | ▪ CYP17A1 | Brænne et al.46, score range 1-11 ▪ NT5C2 (total score = 5) ← ▪ CNNM2 (total score = 4) ← Lempiäinen et al.47, score range 2-54 ▪ CYP17A1 (total score = 34) ← Svishcheva et al.49 ▪ CYP17A1 (one dataset) ▪ CNNM2 (one dataset) ▪ AS3MT (one dataset) | CYP17A1 is the most likely causal gene. |
34 | rs12801636 | 11: 65 391 317 | PCNX3 | ▪ SIPA1 ← ▪ MAP3K11 ← ▪ CTSW ← ← ▪ FIBP ← ← | ▪ RELA | Brænne et al.46, score range 1-11 ▪ RELA (total score = 6) ← ▪ SIPA1 (total score = 4) ← OVOL1 (total score = 2) ← ▪ PCNXL3 (total score = 1) ← Lempiäinen et al.47, score range 2-54 ▪ RELA (total score = 40) ← van der Harst et al.48 ▪ EHBP1L1¶ ← | Evidence is inconsistent. |
35 | rs974819 | 11: 103 660 567 | MIR4693 | ▪ PDGFD ← ▪ RP11-563P16.1 ← | ▪ PDGFD | van der Harst et al.48 ▪ PDGFD¶ ← | PDGFD is the causal gene. |
36 | rs3184504§ | 12: 111 884 608 | SH2B3 (LNK) | ▪ SH2B3 ← ← ▪ TMEM116 ← ▪ ALDH2 ← ▪ MAPKAPK5 ← ▪ RP3-462E2.3 ← | ▪ SH2B3 (LNK) ▪ ATXN2 | Brænne et al.46, score range 1-11 ▪ SH2B3 (total score = 5) ← ← ▪ ATXN2 (total score = 4) ← ← ▪ FLJ21127 (total score = 1) ← ← Lempiäinen et al.47, score range 2-54 ▪ SH2B3 (total score = 14) ← ← Svishcheva et al.49 ▪ ATXN2 (two datasets) ▪ SH2B3 (one dataset) | SH2B3 is the most likely causal gene. ATXN2 might also be involved. |
37 | rs441§ | 12: 112 228 849 | ALDH2 | ▪ TMEM116 ← ▪ ERP29 ← ▪ SH2B3 ▪ ALDH2 ← ▪ MAPKAPK5 ← | ▪ ATXN2 ▪ ALDH2 ▪ MAPKAPK5 | Brænne et al.46, score range 1-11 ▪ ALDH2 (total score = 6) ← ▪ SH2B3 (total score = 5) ← ▪ TMEM116 (total score = 4) ← ▪ BRAP (total score = 4) ← ▪ MAPKAPK5 (total score = 4) ← ▪ HECTD4 (total score = 2) ← ▪ C12ORF30 (total score = 2) ← Svishcheva et al.49 ▪ ATXN2 (two datasets) ▪ TMEM116 (one dataset) ▪ NAA25 (one dataset) | Evidence is inconsistent. |
38 | rs2258287 | 12: 121 454 313 | C12ORF43 | ▪ OASL ← ▪ C12ORF43 ← ▪ COQ5 | ▪ HNF1A | Brænne et al.46, score range 1-11 ▪ HNF1A (total score = 4) ← ← Lempiäinen et al.47, score range 2-54 ▪ C12ORF43 (total score = 8) ← ← | HNF1A is the most likely causal gene. |
39 | rs11057830 | 12: 125 307 053 | SCARB1 | — | ▪ SCARB1 | Brænne et al.46, score range 1-11 ▪ SCARB1 (total score = 6) ← Lempiäinen et al.47, score range 2-54 ▪ SCARB1 (total score = 34) ← ▪ DHX37 (total score = 2) Svishcheva et al.49 ▪ SCARB1 (one dataset) | SCARB1 is the causal gene. |
40 | rs9319428 | 13: 28 973 621 | FLT1 (VEGFR1) | — | ▪ FLT1 (VEGFR1) | Lempiäinen et al.47, score range 2-54 ▪ FLT1 (total score = 34) | FLT1 is the causal gene. |
41 | rs9515203 | 13: 111 049 623 | COL4A2 | — | ▪ COL4A2, COL4A1 | Brænne et al.46, score range 1-11 ▪ IRS2 (total score = 4) Lempiäinen et al.47, score 2-54 ▪ ANKRD10 (total score = 8) ← ▪ COL4A1 (total score = 2) ← ← ▪ COL4A2 (total score = 2) ←, ← ← Svishcheva et al.49 ▪ COL4A2 (two datasets) ▪ COL4A1 (one dataset) | COL4A2 and COL4A1 are the causal genes. |
42 | rs2895811 | 14: 100 133 942 | HHIPL1 | ▪ HHIPL1 | Brænne et al.46, score range 1-11 ▪ YY1 (total score = 6) ← ▪ EML1 (total score = 2) Lempiäinen et al.47, score 2-54 ▪ HHIPL1 (total score = 6) ← | HHIPL1 is the most likely causal gene. | |
43 | rs7178051 | 15: 79 118 296 | ADAMTS7 | ▪ ADAMTS7 ← ▪ CTSH ← ▪ RP11-160C18.2 pseudogene ← ▪ MORF4L1 ← | ▪ ADAMTS7 | Brænne et al.46, score range 1-11 ▪ ADAMTS7 (total score = 7) ← ←, ← ← ← ▪ WDR61 (total score = 2) ← ← Lempiäinen et al.47, score range 2-54 ▪ ADAMTS7 (total score = 38) ← ← ← ▪ CTSH (total score = 8) van der Harst et al.48 ▪ ADAMTS7 ← ← ← ← ▪ RASGRF1 ← ← ← ← Svishcheva et al.49 ▪ ADAMTS7 (two datasets) | ADAMTS7 is the causal gene. |
44 | rs17514846 | 15: 91 416 550 | FURIN | ▪ FURIN ← ▪ FES ← ▪ MAN2A2 ← | ▪ FURIN | Brænne et al.46, score range 1-11 ▪ FURIN (total score = 8) ← ▪ FES (total score = 7) ← ▪ MAN2A2 (total score = 3) ← Lempiäinen et al.47, score range 2-54 ▪ FURIN (total score = 10) ← ▪ FES (total score = 10) ← Svishcheva et al.49 ▪ FURIN (two datasets) ▪ FES (one dataset) | FURIN is the causal gene. FES might also be involved. |
45 | rs1050362 | 16: 72 130 815 | DHX38 | ▪ HP ← ▪ DHX38 ← ▪ DHODH ← ▪ PKD1L3 ← | ▪ HP | Svishcheva et al.49 ▪ HPR (one dataset) | HP is the most likely causal gene. |
46 | rs170041 | 17: 2 170 216 | SMG6 | — | ▪ SMG6 ▪ SRR | Lempiäinen et al.47, score range 2-54 ▪ SRR (total score = 8) Svishcheva et al.49 ▪ SMG6 (two datasets) | Evidence is inconsistent. |
47 | rs12936587 | 17: 17 543 722 | RAI1 | ▪ SREBF1 (SREBP1) ← ▪ PEMT ← | ▪ PEMT ▪ SREBF1 (SREBP1) ▪ MIR33B (hsa-mir-33b) | Lempiäinen et al.47, score range 2-54 ▪ SREBF1 (total score = 40) ← ▪ PEMT (total score = 40) ← | Evidence is inconsistent. PEMT, SREBF1, and MIR33B can be involved. |
48 | rs2070783 | 17: 62 406 971 | PECAM1 | ▪ PECAM1 ← | ▪ PECAM1 | Brænne et al.46, score range 1-11 ▪ PECAM1 (total score = 4) ← ▪ POLG2 (total score = 3) ← | PECAM1 is the causal gene. |
49 | rs12052058 | 19: 11 159 525 | SMARCA4 | ▪ SMARCA4 ← ▪ CARM1 ← ▪ C19ORF52 ← ▪ KANK2 | ▪ LDLR ▪ SMARCA4 ▪ CARM1 | Brænne et al.46, score range 1-11 ▪ KANK2 (total score = 5) ← ← ▪ SMARCA4 (total score = 4) ← ▪ ANKRD25 (total score = 2) ← ← Lempiäinen et al.47, score range 2-54 ▪ LDLR (total score = 35) ← ▪ CARM1 (total score = 40) ←, ← ← ← ▪ SMARCA4 (total score = 40) ←, ← ← ← ▪ C19ORF38 (total score = 10) ← ← ← Svishcheva et al.49 ▪ LDLR (two datasets) ▪ SMARCA4 (one dataset) | LDLR is the causal gene. SMARCA4 and CARM1 might also be involved. |
50 | rs867186 | 20: 33 764 554 | PROCR, MMP24-AS1-EDEM2 | ▪ TRPC4AP ← ▪ EIF6 ← ▪ ITGB4BP ← ▪ EDEM2 ← ← ▪ HS.443185 ← ← | ▪ PROCR (EPCR) | Brænne et al.46, score range 1-11 ▪ PROCR (total score = 8) ← ▪ MYH7B (total score = 5) ← ▪ TRPC4AP (total score = 3) ← ▪ EIF6 (total score = 3) ← ▪ RBL1 (total score = 3) ← ▪ ROMO1 (total score = 2) ← ▪ ITGB4BP (total score = 2) ← ▪ FLJ25841 (total score = 1) ← ▪ MT1P3 (total score = 1) ← van der Harst et al.48 ▪ PROCR¶ ← ▪ TRPC4AP¶ ← ▪ GGT7 ← ▪ EDEM2 ← ▪ NCOA6 ← ▪ HMGB3P1 ← | PROCR is the most likely causal gene. |
51 | rs9982601 | 21: 35 599 128 | LINC00310 | ▪ MRPS6 ▪ KCNE2 | ▪ KCNE2 (MIRP1) | Lempiäinen et al.47, score range 2-54 ▪ SON (total score = 8) van der Harst et al.48 ▪ MRPS6¶ ← ▪ SLC5A3¶ ← | KCNE2 is the most likely causal gene. |
