Table 5.
Top PRSs for the 20 Most Common Cancer Traits in MGI
| PRS Cancer Trait (PheCode) | GWAS Source | Method Tuning Parameter | # SNPs | Brier Score | AAUC (95% CI) | Odds Ratio Continuous PRS (95% CI)a | Odds Ratio Top 1% (95% CI)b |
|---|---|---|---|---|---|---|---|
| Basal cell carcinoma (172.21) | Large GWAS: Chahal et al.49 | P&T: p ≤ 4 × 10−8 | 27 | 0.106 | 0.632 (0.616,0.647) | 1.66 (1.57,1.76) | 3.79 (2.68,5.35) |
| Melanomas of skin (172.1) | UKB GWAS PHECODE | P&T: p ≤ 2 × 10−7 | 15 | 0.0952 | 0.604 (0.587,0.62) | 1.49 (1.4,1.57) | 2.97 (2.04,4.34) |
| Breast cancer [female] (174.1) | Large GWAS: Michailidou et al.11 | Lassosum: s = 0.5, λ = 0.0043 | 118,388 | 0.134 | 0.641 (0.625,0.656) | 1.70 (1.59,1.81) | 2.48 (1.63,3.77) |
| Cancer of prostate (185) | Large GWAS: Schumacher et al.12 | Lassosum: s = 0.5, λ = 0.007 | 26,418 | 0.145 | 0.665 (0.647,0.684) | 1.91 (1.77,2.05) | 4.92 (3.21,7.55) |
| Squamous cell carcinoma (172.22) | GWAS Catalog | P&T: p ≤ 1 × 10−11 | 7 | 0.0977 | 0.593 (0.573,0.613) | 1.45 (1.36,1.55) | 3.74 (2.46,5.68) |
| Cancer of bladder (189.2) | GWAS Catalog | P&T: p ≤ 5 × 10−8 | 13 | 0.0917 | 0.572 (0.55,0.594) | 1.29 (1.2,1.39) | 1.47 (0.779,2.77) |
| Colorectal cancer (153) | Large GWAS: Huyghe et al.15 | P&T: p ≤ 4 × 10−7 | 81 | 0.0828 | 0.553 (0.525,0.577) | 1.21 (1.12,1.32) | 3.04 (1.79,5.17) |
| Colon cancer (153.2) | UKB GWAS PHECODE | Lassosum: s = 0.2, λ = 0.038 | 150 | 0.083 | 0.567 (0.54,0.594) | 1.25 (1.13,1.37) | 1.17 (0.477,2.87) |
| Cancer of bronchus/lung (165.1) | GWAS Catalog | P&T: p ≤ 1 × 10−10 | 14 | 0.0827 | 0.529 (0.503,0.558) | 1.12 (1.01,1.24) | 1.75 (0.796,3.85) |
| Thyroid cancer (193) | GWAS Catalog | P&T: p ≤ 3.2 × 10−10 | 8 | 0.0812 | 0.618 (0.587,0.647) | 1.57 (1.41,1.74) | 5.14 (2.94,8.99) |
| Nodular lymphoma (202.21) | UKB GWAS FINNGEN | Lassosum: s = 1, λ = 0.018 | 2,209,179 | 0.0825 | 0.538 (0.504,0.573) | 1.15 (1.02,1.29) | 1.48 (0.538,4.05) |
| Cancer of brain (191.11) | UKB GWAS ICD10 | Lassosum: s = 0.9, λ = 0.1 | 522 | 0.0824 | 0.546 (0.504,0.587) | 1.20 (1.04,1.37) | 1.42 (0.453,4.47) |
| Cancer of esophagus (150) | UKB GWAS ICD10 | Lassosum: s = 1, λ = 0.078 | 2,001 | 0.0826 | 0.551 (0.51,0.588) | 1.20 (1.04,1.39) | 1.81 (0.56,5.82) |
| Cancer of larynx (149.4) | UKB GWAS ICD10 | Lassosum: s = 0.9, λ = 0.1 | 25,920 | 0.0822 | 0.570 (0.522,0.618) | 1.28 (1.09,1.51) | 2.14 (0.649,7.06) |
| Cancer of other male genital organs (187) | UKB GWAS FINNGEN | P&T: p ≤ 4 × 10−6 | 97 | 0.083 | 0.558 (0.506,0.606) | 1.23 (1.03,1.46) | 1.04 (0.183,5.95) |
| Lymphoid leukemia (204.1) | UKB GWAS FINNGEN | P&T: p ≤ 1 × 10−6 | 6 | 0.0819 | 0.578 (0.517,0.642) | 1.36 (1.11,1.66) | 3.69 (1.01,13.4) |
| Multiple myeloma (204.4) | UKB GWAS ICD10 | P&T: p ≤ 7.9 × 10−6 | 27 | 0.0823 | 0.547 (0.479,0.613) | 1.24 (1,1.53) | 2.6 (0.593,11.4) |
| Cancer of testis (187.2) | UKB GWAS PHESANT | Lassosum: s = 0.9, λ = 0.078 | 771 | 0.084 | 0.656 (0.593,0.717) | 1.67 (1.3,2.14) | 2.72 (0.568,13.1) |
| Hodgkin’s disease (201) | GWAS Catalog | P&T: p ≤ 1 × 10−6 | 20 | 0.0821 | 0.620 (0.559,0.688) | 1.48 (1.15,1.89) | 2.64 (0.572,12.2) |
| Lymphoid leukemia, chronic (204.12) | GWAS Catalog | P&T: p ≤ 7 × 10−6 | 44 | 0.0776 | 0.696 (0.621,0.764) | 2.12 (1.65,2.74) | 12.9 (4.45,37.6) |
Cancer traits are sorted by observed case counts in MGI; references of studies contributing to GWAS Catalog PRSs are listed in Table S4.
a
PRSs were scaled to mean = 0 and SD = 1.
b
Top 1% versus rest.