Table 2.
Summary of results for nevus count/pigmentation/melanoma analyses from the Leeds case-control samples examining the 11 SNPs replicated for melanoma association in this or previous studies. Results are shown for (i) the proportion and significance of log nevus count variation explained by each SNP, adjusted for age and sex among cases and controls (adjusted for case-control status), (ii) the proportion and significance of case-control adjusted pigmentation variation score explained by each SNP, where the score is calculated from factor analysis of 6 correlated pigmentation phenotypes (see Online Methods), (iii) the association with melanoma risk (both as per-allele OR with 95%CI, and by genotype (compared to a baseline of the homozygote for the common allele)).
| Chromosomal Region | Postulated gene | SNP | MAF | % of variation in log nevus count explained by SNP | % of variation in pigmentation explained by SNP | Per-allele OR (95% CI) for risk of melanoma | OR (95% CI) for risk of melanoma with one copy of Minor allele | OR (95% CI) for risk of melanoma with two copies of Minor allele | ||
|---|---|---|---|---|---|---|---|---|---|---|
| R2 | P | R2 | P | |||||||
| 2q33-q34 | CASP8 | rs13016963 | 0.33 | 0.21 | 0.083* | 0.05 | 0.33 | 1.25 (1.07, 1.46) | 1.26 (1.01, 1.56) | 1.56 (1.11, 2.18) |
| 5p15.33 | TERT/CLMPT1L | rs401681 | 0.46 | 0.50 | 0.0070 | 0.13 | 0.11 | 1.08 (0.93, 1.25) | 1.15 (0.90, 1.47) | 1.15 (0.85, 1.55) |
| 5p13.2 | SLC45A2 | rs16891982 | 0.03 | 0.02 | 0.62 | 1.33 | 1.9 × 10−6 | 0.72 (0.44, 1.18) | 0.78 (0.47, 1.30) | NA |
| 6p25-p23 | IRF4 | rs12203592 | 0.24 | 0.21 | 0.084 | 2.76 | 5.6 × 10−12 | 0.80 (0.67, 0.95) | 0.72 (0.58, 0.91) | 0.81 (0.49, 1.35) |
| 9p21 | CDKN2A/MTAP | rs7023329 | 0.49 | 0.29 | 0.047 | 0.02 | 0.55 | 0.86 (0.73, 1.00) | 0.62 (0.47, 0.82) | 0.73 (0.53, 1.01) |
| 11q14-q21 | TYR | rs1393350 | 0.27 | 0.00 | 0.95 | 1.07 | 2.0 × 10−5 | 1.34 (1.14, 1.58) | 1.19 (0.96, 1.49) | 2.12 (1.41, 3.19) |
| 11q22-q23 | ATM | rs1801516 | 0.14 | 0.07 | 0.33 | 0.00 | 0.95 | 0.88 (0.71, 1.09) | 0.93 (0.73, 1.19) | 0.59 (0.29, 1.21) |
| 16q24.3 | MC1R | rs258322 | 0.10 | 0.00 | 0.81 | 4.00 | 9.0 × 10−17 | 1.83 (1.44, 2.32) | 1.71 (1.33, 2.22) | 7.14 (1.70, 29.98) |
| 20q11.2-q12 | ASIP | rs4911442 | 0.13 | 0.07 | 0.34 | 0.93 | 8.2 × 10−5 | 1.35 (1.08, 1.68) | 1.32 (1.03, 1.69) | 2.06 (0.85, 5.00) |
| 21q22.3 | MX2 | rs45430 | 0.38 | 0.00 | 0.80 | 0.05 | 0.32 | 0.90 (0.77, 1.05) | 0.97 (0.77, 1.22) | 0.77 (0.56, 1.07) |
| 22q13.1 | PLA2G6 | rs6001027 | 0.37 | 0.39 | 0.018 | 0.12 | 0.16 | 0.78 (0.66, 0.91) | 0.79 (0.63, 0.90) | 0.60 (0.42, 0.84) |
| TOTAL | 2.33 | 9.83 | ||||||||
p = 0.004 for controls only