Table 2. Loci reaching genome-wide significance in melanoma GWAS.
| SNP | Region | Gene | Maj/Min | Avg. imputation r2 | MAF1 | 23&Me (Stage 1) | MD Anderson (Stage 2) | Meta-Analysis2 | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| P | OR [CI3] |
P | OR [CI3] |
P | OR [CI3] |
||||||
| rs1805007 | 16q24.3 | MC1R | C/T | 1.00 | 0.07 | 3.8 × 10−28 | 1.47 [1.38, 1.57] |
4.88 × 10-8 | 1.72 [1.41,2.09,] |
4.24 × 10-37 | 1.50 [1.41,1.59] |
| rs35407 | 5p13.2 | SLC45A2 | G/A | 0.98 | 0.03 | 5.6 × 10−22 | 0.46 [0.39, 0.55] |
6.44 × 10-3 | 0.57 [0.38,0.85] |
3.42 × 10-19 | 0.48 [0.41,0.56] |
| rs6059655 | 20q11.22 | RALY-ASIP | G/A | 0.99 | 0.07 | 3.1 × 10−18 | 1.37 [1.28, 1.46] |
1.02 × 10-4 | 1.44 [1.20,1.74] |
5.04 × 10-23 | 1.38 [1.29,1.47] |
| rs201131773 | 9p21.3 | MTAP | I/D | 0.99 | 0.48 | 2.4 × 10−17 | 1.19 [1.15, 1.24] |
- | - | 2.5 × 10−17 | 1.19 [1.15,1.24] |
| rs62389423 | 6p25.3 | IRF4-[]--EXOC2 | G/A | 0.78 | 0.14 | 9.7 × 10−13 | 1.26 [1.18, 1.34] |
7.77 × 10-2 | 1.15 [0.98,,1.34] |
9.14 × 10-14 | 1.24 [1.17,1.31] |
| rs139996880 | 5p15.33 | TERT | G/A | 0.65 | 0.16 | 2.4 × 10−11 | 1.25 [1.18, 1.34] |
0.48* | 1.06* [0.90,1.26] |
7.16 × 10-12 | 1.26 [1.18,1.34] |
| rs1393350 | 11q14.3 | TYR | G/A | 1.00 | 0.27 | 2.7 × 10−11 | 1.17 [1.11, 1.22] |
8.47 × 10-3 | 1.18 [1.04,1.33] |
3.65 × 10-13 | 1.17 [1.12,1.22] |
| rs45430 | 21q22.3 | MX2 | T/C | 1.00 | 0.34 | 1.1 × 10−7 | 0.89 [0.85, 0.93] |
0.11 | 0.91 [0.82,1.02] |
2.89 × 10-8 | 0.89 [0.86,0.93] |
| rs187843643 | 5p15.1 | BASP1---[]** | C/T | 0.74 | 0.01 | 6.0 × 10−7 | 1.96 [1.54,2.50] |
0.52 | 1.69 [0.34,8.38] |
3.53 × 10-8 | 1.96 [1.54,2.48] |
SNPs that met genome-wide significance (P < 5 × 10−8) in the overall meta-analysis are listed. Additionally, we report genetic locus, nearest genes, major allele, minor allele, minor allele frequency (MAF) in stage 1 controls, average imputation r2 (a measure of imputation quality) for stage 1, and odds ratio (OR) with P value for each stage, calculated with respect to the minor allele. Stage 1 included 4,842 melanoma cases and 286,565 controls from 23andMe. Stage 2 included 1,804 melanoma cases and 1,026 controls from the MD Anderson Cancer Center. The combined fixed-effect meta-analysis, totaled 6,628 melanoma cases and 287,591 controls. Statistics for effect heterogeneity (Phet and I2) are included in Supplementary Table 4. All subjects were from the US and of European ancestry.
1MAF = minor allele frequency in stage 1 controls
2Meta-analysis = Combined 23&Me + MD Anderson
3CI = 95% confidence interval
** = Not previously associated with melanoma risk
* = Imputation r2 = 0.2968 in MD Anderson Dataset.