Table 3.
Colocalized loci for CVDs-CeVDs-RFs triplets
| Loci information | Traits combination and MOLOC results | SNPs and genes annotation | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. | CHR | Band | Min pos | Max pos | CVD | CeVD | RF | PPA | Best SNP | Most severe consequence | CADD score | RegulomeDB ranking | Gene mapping by L2G | Gene mapping by V2G |
| 1 | 1 | 1p36.22 | 10,763,241 | 10,802,977 | CAD | AS | SBP | 0.98 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 |
| 1 | 1p36.22 | 10,787,538 | 10,802,977 | CAD | AS | TG | 0.97 | rs880315 | intron_variant | 8.97 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,873,382 | CAD | AS | LDL-C | 0.97 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,763,241 | 10,802,977 | CAD | AIS | SBP | 0.98 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,802,977 | CAD | AIS | TG | 0.97 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,873,382 | CAD | AIS | LDL-C | 0.96 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,771,488 | 10,802,468 | AF | AS | SBP | 1.00 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,802,468 | AF | AS | TG | 1.00 | rs880315 | intron_variant | 8.97 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,802,468 | AF | AS | LDL-C | 0.99 | rs880315 | intron_variant | 8.97 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,771,488 | 10,802,468 | AF | AIS | SBP | 1.00 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,802,468 | AF | AIS | TG | 0.99 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 1 | 1p36.22 | 10,787,538 | 10,802,468 | AF | AIS | LDL-C | 0.99 | rs17035646 | intron_variant | 6.41 | 4 | CASZ1 | CASZ1 | |
| 2 | 6 | 6p21.2 | 36,616,698 | 36,659,932 | HF | AS | TG | 0.92 | rs4151702 | intron_variant | 5.17 | 5 | CDKN1A | CDKN1A |
| 6 | 6p21.2 | 36,616,698 | 36,659,932 | HF | AIS | TG | 0.94 | rs4135240 | intron_variant | 7.95 | 2b | CDKN1A | CDKN1A | |
| 6 | 6p21.2 | 36,613,812 | 36,659,932 | AF | AS | TG | 0.96 | rs4151702 | intron_variant | 5.17 | 5 | CDKN1A | CDKN1A | |
| 6 | 6p21.2 | 36,613,812 | 36,659,932 | AF | AIS | TG | 0.95 | rs4151702 | intron_variant | 5.17 | 5 | CDKN1A | CDKN1A | |
| 3 | 7 | 7p21.1 | 18,983,174 | 19,064,300 | CAD | AS | SBP | 1.00 | rs2107595 | regulatory_region_variant | 18.10 | 2b | TWIST1 | TWIST1 |
| 7 | 7p21.1 | 18,983,174 | 19,064,300 | CAD | AIS | SBP | 1.00 | rs2107595 | regulatory_region_variant | 18.10 | 2b | TWIST1 | TWIST1 | |
| 7 | 7p21.1 | 18,986,970 | 19,062,130 | MI | AS | SBP | 1.00 | rs2107595 | regulatory_region_variant | 18.10 | 2b | TWIST1 | TWIST1 | |
| 7 | 7p21.1 | 18,985,270 | 19,062,130 | MI | AIS | SBP | 1.00 | rs2107595 | regulatory_region_variant | 18.10 | 2b | TWIST1 | TWIST1 | |
| 4 | 9 | 9p21.3 | 21,675,670 | 22,202,907 | CAD | AS | LDL-C | 0.84 | rs2891168 | intron_variant | 3.47 | 4 | CDKN2B | CDKN2B |
| 9 | 9p21.3 | 21,675,670 | 22,202,907 | CAD | AIS | LDL-C | 0.83 | rs2891168 | intron_variant | 3.47 | 4 | CDKN2B | CDKN2B | |
| 9 | 9p21.3 | 21,683,805 | 22,137,685 | MI | AS | LDL-C | 0.83 | rs2891168 | intron_variant | 3.47 | 4 | CDKN2B | CDKN2B | |
| 9 | 9p21.3 | 21,683,805 | 22,137,685 | MI | AIS | LDL-C | 0.81 | rs2891168 | intron_variant | 3.47 | 4 | CDKN2B | CDKN2B | |
| 9 | 9p21.3 | 21,997,872 | 22,125,913 | HF | AS | LDL-C | 0.90 | rs7859727 | intron_variant | 1.45 | 3a | CDKN2B | CDKN2B | |
| 9 | 9p21.3 | 21,997,872 | 22,125,913 | HF | AIS | LDL-C | 0.93 | rs7859727 | intron_variant | 1.45 | 3a | CDKN2B | CDKN2B | |
| 5 | 9 | 9q34.2 | 136,121,623 | 136,384,162 | CAD | AS | TG | 0.98 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO |
| 9 | 9q34.2 | 136,121,623 | 136,384,162 | CAD | AS | HDL-C | 0.99 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,121,623 | 136,384,162 | CAD | AIS | TG | 0.98 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136121623 | 136384162 | CAD | AIS | HDL-C | 0.99 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,128,259 | 136,541,229 | MI | AS | TG | 0.98 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,042,324 | 136,541,229 | MI | AS | HDL-C | 0.99 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,128,259 | 136,541,229 | MI | AIS | TG | 0.98 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,042,324 | 136,541,229 | MI | AIS | LDL-C | 0.80 | rs2519093 | intron_variant | 7.47 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,042,324 | 136,541,229 | MI | AIS | HDL-C | 0.99 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,137,065 | 136,155,000 | HF | AS | SBP | 0.81 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,137,065 | 136,296,530 | HF | AS | TG | 0.92 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,137,065 | 136,296,530 | HF | AS | HDL-C | 0.95 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,137,065 | 136,155,000 | HF | AIS | SBP | 0.82 | rs635634 | upstream_gene_variant | 2.34 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136137065 | 136,296,530 | HF | AIS | TG | 0.96 | rs532436 | intron_variant | 3.46 | 3a | ABO | ABO | |
| 9 | 9q34.2 | 136,137,065 | 136,155,444 | HF | AIS | LDL-C | 0.82 | rs2519093 | intron_variant | 7.47 | 4 | ABO | ABO | |
| 9 | 9q34.2 | 136,137,065 | 136,296,530 | HF | AIS | HDL-C | 0.96 | rs532436 | intron_variant | 3.46 | 3a | ABO | ABO | |
| 6 | 11 | 11p15.4 | 9,750,757 | 9,822,520 | MI | AIS | SBP | 0.87 | rs360153 | non_coding_transcript_exon_variant | 0.73 | 4 | SWAP70 | SWAP70 |
| 7 | 12 | 12q24.12 | 111,281,636 | 113,235,279 | CAD | AS | SBP | 0.96 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 |
| 12 | 12q24.12 | 111,281,636 | 113,486,539 | CAD | AS | LDL-C | 0.98 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,281,636 | 113,486,539 | CAD | AS | HDL-C | 0.98 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,281,636 | 113,235,279 | CAD | AIS | SBP | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,281,636 | 113,486,539 | CAD | AIS | LDL-C | 0.98 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,281,636 | 113,486,539 | CAD | AIS | HDL-C | 0.98 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,359,712 | 113,112,650 | MI | AS | SBP | 0.95 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,359,712 | 113,030,227 | MI | AS | LDL-C | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111359712 | 113,030,227 | MI | AS | HDL-C | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,359,712 | 113,112,650 | MI | AIS | SBP | 0.96 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,359,712 | 113,030,227 | MI | AIS | LDL-C | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111359712 | 113,030,227 | MI | AIS | HDL-C | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111426615 | 113,024,793 | HF | AS | SBP | 0.95 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,426,615 | 113,024,793 | HF | AS | LDL-C | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,426,615 | 112,985,328 | HF | AS | HDL-C | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,426,615 | 113,024,793 | HF | AIS | SBP | 0.97 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,426,615 | 113,024,793 | HF | AIS | LDL-C | 0.98 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 12 | 12q24.12 | 111,426,615 | 112,985,328 | HF | AIS | HDL-C | 0.98 | rs3184504 | missense_variant | 11.21 | 3a | SH2B3 | SH2B3 | |
| 8 | 13 | 13q14.13 | 47,067,841 | 47,314,172 | AF | AS | SBP | 0.91 | rs1535791 | intron_variant | 17.94 | 6 | LRCH1 | LRCH1 |
| 13 | 13q14.13 | 47,154,966 | 47,290,530 | AF | AS | TG | 0.88 | rs1535791 | intron_variant | 17.94 | 6 | LRCH1 | LRCH1 | |
| 13 | 13q14.13 | 47,154,966 | 47,290,530 | AF | AS | HDL-C | 0.92 | rs1535791 | intron_variant | 17.94 | 6 | LRCH1 | LRCH1 | |
| 13 | 13q14.13 | 47,154,966 | 47,323,718 | AF | AIS | SBP | 0.89 | rs9534454 | intron_variant | 0.68 | 4 | LRCH1 | LRCH1 | |
| 13 | 13q14.13 | 47,154,966 | 47,323,718 | AF | AIS | TG | 0.87 | rs4942561 | intron_variant | 0.68 | 7 | LRCH1 | LRCH1 | |
| 13 | 13q14.13 | 47,154,966 | 47,290,530 | AF | AIS | HDL-C | 0.90 | rs4942561 | intron_variant | 0.68 | 7 | LRCH1 | LRCH1 | |
| 9 | 15 | 15q26.1 | 91,392,256 | 91,443,059 | MI | AS | SBP | 0.94 | rs4932373 | intron_variant | 4.48 | 4 | FES | FES |
| 15 | 15q26.1 | 91,392,256 | 91,443,059 | MI | AIS | SBP | 0.96 | rs35346340 | splice_region_variant | 7.74 | 2b | FES | FES | |
| 15 | 15q26.1 | 91,392,256 | 91,443,059 | MI | AIS | LDL-C | 0.91 | rs35346340 | splice_region_variant | 7.74 | 2b | FES | FES | |
| 10 | 17 | 17q21.31 | 43,463,493 | 45,244,074 | AF | AIS | cIMT | 0.99 | rs76774446 | intron_variant | 0.35 | 2b | GOSR2 | RPRML |
| 11 | 19 | 19p13.2 | 10,396,065 | 11,526,765 | CAD | AS | LDL-C | 0.87 | rs73015024 | upstream_gene_variant | 1.34 | 7 | LDLR | LDLR |
| 19 | 19p13.2 | 10,643,471 | 11,526,765 | CAD | AS | cIMT | 0.87 | rs55997232 | regulatory_region_variant | 6.34 | 4 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,643,471 | 11,526,765 | CAD | AS | cIMT | 0.87 | rs55997232 | regulatory_region_variant | 6.34 | 4 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,643,471 | 11,526,765 | CAD | AIS | cIMT | 0.82 | rs55997232 | regulatory_region_variant | 6.34 | 4 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,643,471 | 11,526,765 | CAD | AIS | cIMT | 0.82 | rs55997232 | regulatory_region_variant | 6.34 | 4 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,593,429 | 11,523,844 | MI | AS | LDL-C | 0.85 | rs73015024 | upstream_gene_variant | 1.34 | 7 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,727,014 | 11,523,844 | MI | AS | cIMT | 0.86 | rs112374545 | intergenic_variant | 1.04 | 6 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,727,014 | 11,523,844 | MI | AS | cIMT | 0.86 | rs112374545 | intergenic_variant | 1.04 | 6 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,727,014 | 11,523,844 | MI | AIS | cIMT | 0.81 | rs112374545 | intergenic_variant | 1.04 | 6 | LDLR | LDLR | |
| 19 | 19p13.2 | 10,727,014 | 11,523,844 | MI | AIS | cIMT | 0.81 | rs112374545 | intergenic_variant | 1.04 | 6 | LDLR | LDLR | |
This table shows the shared genetic loci and annotation for the MOLOC results. The PPA for each CVD-CeVD-RF combination was obtained for each locus, and the best colocalized SNP was further identified. Positional and functional annotations using CADD score, RegulomeDB ranking, L2G (Locus-to-Gene), and V2G (Variant-to-Gene) were performed.
MOLOC multiple-trait colocalization, PPA posterior probability of association, CVD cardiovascular disease, CeVD cerebrovascular disease, RF risk factor, CHR the number of chromosomes, Min pos the minimum position of the locus, Max pos the maximum position of the locus, PPA posterior probability of association, CADD score combined annotation dependent depletion score, L2G locus-to-gene, V2G variant-to-gene.