Table 1:
Description of leading studies used to develop and validate various CAD PRS models
| Derivation | Target | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Discovery GWAS | Training/Testing | Validation | ||||||||||||
| Method | Description | Cohort | Ncase | Ncontrol | PRS (NSNP) | Cohort | Ncase | Ncontrol | Ref | Cohort | Ncase or Ntreatment | Ncontrol or Nplacebo | Performance | Ref |
| P+T | pruning and p-value thresholding | CARDIoGRAMplusC4D | 22,333 | 64,762 | PRSMega (27) | community case: MDCS 1st prevention: JUPITER, ASCOT-LLA 2nd prevention: CARE, PROVE-IT |
3,477 | 44,944 | 67 | FOURIER | 7,163 | 7,135 | 6 | |
| ODYSSEY | 9,462 | 9,462 | 72 | |||||||||||
| CARDIoGRAMplusC4D | 22,333 | 64,762 | PRSTada (50) | Malmö Diet and Cancer study (MDCS) | 2,213 | 21,382 | 69 | ARIC | 1,230 | 6,584 | HR: 1.75 (1.46–2.10) | 66 | ||
| WGHS | 971 | 20,251 | HR: 1.94 (1.58–2.39) | |||||||||||
| MDCS | 2,903 | 19,486 | HR: 1.98 (1.76–2.23) | |||||||||||
| eMERGE Phase III (European) | 5,887 | 39,758 | OR: 1.28 (1.25–1.32) HR: 1.20 (1.15–1.25) |
73 | ||||||||||
| eMERGE Phase III (African) | 527 | 7,070 | OR: 1.05 (0.98–1.14) HR: 1.05 (0.94–1.17) |
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| eMERGE Phase III (Hispanic) | 299 | 2,194 | OR: 1.20 (1.05–1.35) HR: 1.13 (0.93–1.36) |
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| CADIoGRAMplusC4D | 63,746 | 130,681 | PRSNataragan (57) | WOSCOPS | 604 | 4,288 | 68 | ODYSSEY | 9,462 | 9,462 | 72 | |||
| JUPITER | 108 | 8603 | ||||||||||||
| ASCOT-LLA | 4070 | 149 | ||||||||||||
| CARDIA | 1154 | |||||||||||||
| BioImage | 4392 | |||||||||||||
| LDpred | Bayesian PRS method adjusting marginal SNP effect size with LD reference | CADIoGRAMplusC4D | 63,746 | 130,681 | PRSKhera (6,630,150) | UK Biobank Phase II | 8,676 | 260,302 | 61 | MHI Biobank Phase 1 (IcWGS) | 974 | 976 | CAD Prevalence OR: 1.64 (1.48–1.81) | 77 |
| WHI Biobank Phase 2 (array) | 2,492 | 817 | CAD Prevalence OR: 1.55 (1.38–1.73) | |||||||||||
| CARTaGENE | 173 | 5,589 | CAD Prevalence OR: 1.69 (1.44–1.99) | |||||||||||
| MDCS | 4,122 | 24,434 | HR: 1.45 (1.40–1.49) | 75 | ||||||||||
| eMERGE Phase III (European) | 5,887 | 39,758 | OR: 1.66 (1.62–1.71) HR: 1.50 (1.43–1.56) |
73 | ||||||||||
| eMERGE Phase III (African) | 527 | 7,070 | OR: 1.30 (1.21–1.41) HR: 1.19 (1.07–1.33) |
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| eMERGE Phase III (Hispanic) | 299 | 2,194 | OR: 1.42 (1.25–1.61) HR: 1.16 (0.96–1.41) |
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| Meta-analysis | reciprocal two-stage sequential discovery and replication design with independent SNPs | CADIoGRAMplusC4D | 88,192 | 162,544 | 161 | UK Biobank | 34,541 | 261,984 | 57 | |||||
| UK Biobank | 34,541 | 261,984 | ||||||||||||
| Meta-analysis | meta-score based on 3 previous scores | CARDIoGRAMplusC4D | 63,746 | 130,681 | PRSInouye (1,745,179) | UK Biobank | 22,242 | 460,387 | 70 | MHI Biobank Phase 1 (IcWGS) | 974 | 976 | CAD Prevalence OR: 1.74 (1.57–1.93) | 77 |
| WHI Biobank Phase 2 (array) | 2,492 | 817 | CAD Prevalence OR: 1.60 (1.43–1.80) | |||||||||||
| WTCCC-CAD | 1,926 | 2,938 | CARTaGENE | 173 | 5,589 | CAD Prevalence OR: 1.75 (1.49–2.05) | ||||||||
| eMERGE Phase III (European) | 5,887 | 39,758 | OR: 1.73 (1.68–1.78) HR: 1.53 (1.46–1.60) |
73 | ||||||||||
| MIGEN-Harps | 488 | 531 | eMERGE Phase III (African) | 527 | 7,070 | OR: 1.40 (1.30–1.52) HR: 1.27 (1.13–1.43) |
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| eMERGE Phase III (Hispanic) | 299 | 2,194 | OR: 1.93 (1.67–2.22) HR: 1.53 (1.23–1.90) |
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| Trans-ancestry meta-GWAS | fixed-effect and random-effect meta-analyses | CARDIoGRAMplusC4D | 60,801 | 123,504 | PRSKoyama (75,028) | Independent Japanese cohort | 1,827 | 9,172 | 58 | |||||
| UK Biobank | 34,541 | 261,984 | ||||||||||||
| Biobank Japan | 25,892 | 142,336 | ||||||||||||
| AnnoPred | Bayesian PRS framework leveraging functional annotation | UK Biobank | 4,746 | 88,182 | PRSYe (2,994,054) | UK Biobank | 3,467 | 172,771 | 107 | |||||
| SCT | stacked clumping and thresholding | UK Biobank | 7,912 | 121,941 | PRSBolli (300,238) | UK Biobank | 15,433 | 262,900 | 108 | |||||