Table 1. Top 40 SNPs in BPC3 and associations with aggressive prostate cancer in BPC3, PRACTICAL, and random-effects meta-analysis.
| SNP | Alleles | Region | Trait in GWAS catalog | BPC3 | PRACTICAL | Meta-analysis | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | p value | OR (95% CI) | p value | OR (95% CI) | p value | phet | I2 (%) | ||||
| rs7014346 | A vs G | 8q24.21 | Colorectal cancer | 1.19 (1.11–1.28) | 1.60 × 10−6 | 1.22 (1.16–1.29) | 3.49 × 10−13 | 1.21 (1.16–1.27) | 3.22 × 10−18 | 0.64 | 0 |
| rs6569648 | C vs T | 6q23.1 | Height | 0.86 (0.79–0.93) | 3.08 × 10−4 | 0.97 (0.91–1.04) | 4.16 × 10−1 | 0.92 (0.81–1.04) | 0.175 | 0.02 | 82.8 |
| rs2687720a | A vs G | 3q21.3 | Menarche (age at onset) | 1.15 (1.07–1.24) | 3.48 × 10−4 | 1.09 (1.03–1.16) | 4.02 × 10−3 | 1.11 (1.06–1.17) | 6.74 × 10−5 | 0.26 | 19.8 |
| rs10505477 | C vs T | 8q24.21 | Colorectal cancer | 0.85 (0.77–0.93) | 4.15 × 10−4 | 0.79 (0.75–0.83) | 7.72 × 10−20 | 0.81 (0.76–0.86) | 3.56 × 10−11 | 0.21 | 35.4 |
| rs9318086 | A vs G | 13q12.12 | Myopia | 1.13 (1.06–1.22) | 4.53 × 10−4 | 1.01 (0.96–1.06) | 7.38 × 10−1 | 1.07 (0.95–1.20) | 2.65 × 10−1 | <0.01 | 85.2 |
| rs753955 | T vs C | 13q12.12 | Lung cancer | 1.14 (1.06–1.22) | 4.60 × 10−4 | 1.03 (0.98–1.09) | 2.74 × 10−1 | 1.08 (0.98–1.19) | 1.18 × 10−1 | 0.03 | 77.9 |
| rs3180018 | A vs G | 1q22 | Crohn disease | 1.16 (1.07–1.25) | 5.15 × 10−4 | 0.99 (0.93–1.05) | 7.47 × 10−1 | 1.07 (0.92–1.24) | 4.02 × 10−1 | <0.01 | 88.7 |
| rs10069690 | C vs T | 5p15.33 | Breast cancer | 1.21 (1.08–1.35) | 6.10 × 10−4 | 1.20 (1.13–1.28) | 3.45 × 10−9 | 1.21 (1.14–1.27) | 8.82 × 10−12 | 0.97 | 0 |
| rs6910071 | G vs A | 6p21.32 | Rheumatoid arthritis | 1.16 (1.06–1.27) | 8.53 × 10−4 | 1.02 (0.96–1.09) | 5.67 × 10−1 | 1.08 (0.95–1.23) | 2.16 × 10−1 | 0.02 | 81.8 |
| rs7788750a | T vs C | 7q22.1 | Ulcerative colitis | 1.36 (1.13–1.63) | 9.83 × 10−4 | 0.88 (0.76–1.00) | 5.39 × 10−2 | 1.09 (0.71–1.67) | 7.10 × 10−1 | <0.01 | 93.1 |
| rs2315008 | T vs G | 20q13.33 | Inflammatory bowel disease | 0.88 (0.82–0.95) | 1.15 × 10−3 | 0.86 (0.81–0.91) | 1.45 × 10−7 | 0.87 (0.83–0.91) | 7.43 × 10−10 | 0.57 | 0 |
| rs6756629 | A vs G | 2p21 | Total and LDL cholesterol | 1.26 (1.09–1.44) | 1.20 × 10−3 | 0.96 (0.86–1.07) | 4.49 × 10−1 | 1.09 (0.84–1.42) | 5.07 × 10−1 | <0.01 | 89 |
| rs4809330 | A vs G | 20q13.33 | Crohn disease | 0.88 (0.82–0.95) | 1.21 × 10−3 | 0.86 (0.81–0.91) | 1.77 × 10−7 | 0.87 (0.83–0.91) | 9.50 × 10−10 | 0.57 | 0 |
| rs3764021 | A vs G | 12p13.31 | Type 1 diabetes | 0.89 (0.82–0.95) | 2.04 × 10−3 | 1.02 (0.97–1.07) | 4.91 × 10−1 | 0.95 (0.83–1.09) | 4.91 × 10−1 | <0.01 | 88.3 |
| rs10229583 | A vs G | 7q32.1 | Type 2 diabetes | 1.14 (1.05–1.23) | 2.10 × 10−3 | 1.02 (0.96–1.08) | 5.45 × 10−1 | 1.07 (0.96–1.19) | 1.99 × 10−1 | 0.04 | 77.4 |
| rs968451 | T vs G | 22q13.1 | Primary biliary cirrhosis | 1.15 (1.05–1.26) | 2.24 × 10−3 | 1.02 (0.95–1.09) | 5.82 × 10−1 | 1.08 (0.96–1.21) | 2.10 × 10−1 | 0.04 | 77.5 |
| rs12563627a | T vs C | 1q22 | Inflammatory bowel disease | 1.12 (1.04–1.21) | 2.61 × 10−3 | 1.02 (0.96–1.08) | 5.20 × 10−1 | 1.07 (0.97–1.17) | 1.91 × 10−1 | 0.04 | 75.9 |
| rs10466829 | G vs A | 12p13.31 | Multiple sclerosis | 1.11 (1.04–1.20) | 2.69 × 10−3 | 0.99 (0.94–1.04) | 6.52 × 10−1 | 1.05 (0.93–1.18) | 4.50 × 10−1 | <0.01 | 85.7 |
| rs8079702 | G vs A | 17q24.3 | Primary tooth development (number of teeth) | 1.11 (1.04–1.20) | 3.02 × 10−3 | 0.96 (0.91–1.01) | 1.40 × 10−1 | 1.03 (0.89–1.19) | 6.69 × 10−1 | <0.01 | 90.6 |
| rs2048327 | G vs A | 6q25.3 | Coronary heart disease | 1.12 (1.04–1.20) | 3.06 × 10−3 | 1.05 (1.00–1.11) | 5.69 × 10−2 | 1.08 (1.02–1.14) | 6.00 × 10−3 | 0.22 | 33.4 |
| rs4905994a | T vs C | 14q32.2 | Platelet counts | 1.12 (1.04–1.21) | 3.37×10−3 | 0.96 (0.91–1.02) | 1.83×10−1 | 1.04 (0.89–1.20) | 6.42 × 10−1 | <0.01 | 89.9 |
| rs7901695 | C vs T | 10q25.2 | Type 2 diabetes | 0.89 (0.83–0.96) | 3.67 × 10−3 | 1.00 (0.94–1.06) | 9.89 × 10−1 | 0.95 (0.85–1.06) | 3.39 × 10−1 | 0.02 | 81.4 |
| rs3846662 | C vs T | 5q13.3 | Total and LDL cholesterol | 0.90 (0.84–0.97) | 4.04 × 10−3 | 1.04 (0.98–1.10) | 1.71 × 10−1 | 0.97 (0.85–1.11) | 6.58 × 10−1 | <0.01 | 89.7 |
| rs625658a | A vs C | 1q22 | Inflammatory bowel disease | 1.12 (1.04–1.20) | 4.05 × 10−3 | 1.02 (0.97–1.08) | 4.87 × 10−1 | 1.06 (0.97–1.16) | 1.73 × 10−1 | 0.06 | 72.1 |
| rs6569992 | A vs G | 6q23.3 | Red blood cell traits | 0.88 (0.80–0.96) | 4.24 × 10−3 | 0.93 (0.87–1.00) | 5.68 × 10−2 | 0.91 (0.86–0.96) | 1.00 × 10−3 | 0.32 | 100 |
| rs10033464 | T vs G | 4q25 | Atrial fibrillation | 1.19 (1.06–1.33) | 4.25 × 10−3 | 0.95 (0.87–1.04) | 2.69 × 10−1 | 1.06 (0.85–1.31) | 6.07 × 10−1 | <0.01 | 88.5 |
| rs1562990 | C vs A | 11q12.2 | Alzheimer disease | 1.11 (1.03–1.19) | 5.05 × 10−3 | 1.02 (0.96–1.07) | 5.35 × 10−1 | 1.06 (0.97–1.15) | 1.86 × 10−1 | 0.06 | 71.4 |
| rs4869272a | C vs T | 5q15 | Fasting glucose-related traits | 1.11 (1.03–1.20) | 5.33 × 10−3 | 1.01 (0.95–1.08) | 7.49 × 10−1 | 1.06 (0.96–1.17) | 2.34 × 10−1 | 0.06 | 71.7 |
| rs7903146 | T vs C | 10q25.2 | Type 2 diabetes; Fasting glucose-related traits; Fasting insulin-related traits; Proinsulin levels; HbA1c levels | 0.89 (0.83–0.97) | 5.40 × 10−3 | 1.00 (0.94–1.06) | 9.64 × 10−1 | 0.95 (0.85–1.06) | 3.33 × 10−1 | 0.03 | 79.3 |
| rs2970818 | T vs A | 12p13.32 | Phosphorus levels | 0.83 (0.73–0.95) | 5.42 × 10−3 | 0.98 (0.89–1.07) | 6.26 × 10−1 | 0.91 (0.77–1.06) | 2.31 × 10−1 | 0.05 | 75.1 |
| rs16844874a | C vs T | 2q34 | Glycine | 1.16 (1.05–1.29) | 5.44 × 10−3 | 1.11 (1.04–1.18) | 2.18 × 10−3 | 1.12 (1.06–1.19) | 4.67 × 10−5 | 0.46 | 0 |
| rs4374383 | A vs G | 2q13 | Hepatitis C–induced liver fibrosis | 1.11 (1.03–1.19) | 5.63 × 10−3 | 1.00 (0.93–1.07) | 9.20 × 10−1 | 1.05 (0.95–1.17) | 3.56 × 10−1 | 0.04 | 76.7 |
| rs9900242a | A vs G | 17q24.3 | Pulmonary function in smokers | 0.90 (0.84–0.97) | 5.67 × 10−3 | 0.90 (0.85–0.95) | 1.39 × 10−4 | 0.90 (0.86–0.94) | 2.50 × 10−6 | 0.94 | 0 |
| rs9303521 | T vs G | 17q21.31 | Bone mineral density | 0.90 (0.84–0.97) | 5.42 × 10−3 | 0.99 (0.94–1.04) | 6.26 × 10−1 | 0.95 (0.87–1.04) | 2.35 × 10−1 | 0.05 | 74.1 |
| rsl0804533a | T vs C | 3ql3.32 | Menarche (age at onset) | 0.91 (0.85–0.97) | 5.93 × 10−3 | 1.04 (0.98–1.09) | 1.93 × 10−1 | 0.97 (0.85–1.11) | 6.57 × 10−1 | <0.01 | 88.7 |
| rsl0757274 | A vs G | 9p21.3 | Coronary heart disease | 0.91 (0.85–0.97) | 6.64 × 10−3 | 1.03 (0.98–1.09) | 2.31 × 10−1 | 0.97 (0.85–1.10) | 6.39 × 10−1 | <0.01 | 88 |
| rsl 6948098 | A vs G | 15ql5.3 | Serum albumin level | 0.79 (0.66–0.94) | 5.42 × 10−3 | 0.94 (0.81–1.08) | 6.26 × 10−1 | 0.87 (0.73–1.03) | 9.80 × 10−2 | 0.13 | 56.8 |
| rs944797 | CvsT | 9p21.3 | Coronary heart disease | 1.10(1.03–1.18) | 7.01 × 10−3 | 0.97 (0.92–1.03) | 2.89 × 10−1 | 1.03 (0.91–1.17) | 6.11 × 10−1 | <0.01 | 87.2 |
| rsl0757278 | G vs A | 9p21.3 | Myocardial infarction | 1.11 (1.03–1.19) | 5.42 × 10−3 | 0.98 (0.93–1.03) | 6.26 × 10−1 | 1.04(0.92–1.17) | 5.60 × 10−1 | <0.01 | 86.2 |
| rs9510787 | G vs A | 13ql2.12 | Nasopharyngeal carcinoma | 1.11 (1.03–1.21) | 7.18 × 10−3 | 1.00(0.94–1.07) | 9.82 × 10−1 | 1.05 (0.95–1.17) | 3.47 × 10−1 | 0.04 | 77.5 |
BPC3 = Breast and Prostate Cancer Cohort Consortium; HbAlc = glycated hemoglobin; LDL = low-density lipoprotein; OR = odds ratio; CI = confidence interval; PRACTICAL = Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome; SNP = single-nucleotide polymorphism; GWAS = genome-wide association studies; phet = p value for Cochran's Q statistic for between-study heterogeneity.
Logistic regression was applied in BPC3 and PRACTICAL. Meta-analysis was performed under a random-effects model. All ORs are per-copy of the first allele shown in the Alleles column.
a
These SNPs are correlated with GWAS catalog-indexed SNPs not found in BPC3 per se as follows: rs9900242 and rsl 1654749 (r2 = 0.93, D′ = 1); rs2687720 and rs2687729 (r2 = 1, D′ = l), rsl0804533 and rs6438424 (r2 = 1, D′ = 1), rs7788750 and rs7809799 (r2 = 1, D′ = 1), rsl2563627 and rs670523 (r2 = 0.97, D′ = 1), rs4905994 and rs7149242 (r2 = 0.96, D′ = 1), rs625658 and rs670523 (r2 = 1, D′ = 1), rsl6844874 and rs2216405 (r2 = 0.94, D′ = 1), rs4869272 and rsl3179048 (r2 = 1, D′ = 1).