Table 1.
Genome-wide results for the most significant regions together with follow-up results. SNPs in the most significant regions are listed with their chromosome and position (in base-pair range) and the minor allele. Minor allele frequencies (MAF) are shown for the all controls genotyped genome-wide and in the combined replication sets, where appropriate.
| GENOME-WIDE PHASE | REPLICATION PHASE: GenoMEL + Leeds Case- control |
OVERALL: GENOME-WIDE + REPLICATION |
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|---|---|---|---|---|---|---|---|---|
| SNP with base-pair range |
Minor allele |
MAF | P | OR [Conf. Int.] | P | OR [Conf. Int.] | P | OR [Conf. Int.] |
| Chromosomal Regions Considered for Followup on Basis of This Study | ||||||||
|
Chromosome 9: 21737803-21806528 |
||||||||
| rs4636294 | G | 0.51 | 1.77E-05 | 0.83 [0.76, 0.90] | 0.032 | 0.90 [0.83, 0.99] | 1.97E-06 | 0.86 [0.81, 0.92] |
| rs2218220 | T | 0.51 | 1.85E-05 | 0.83 [0.76, 0.90] | 0.046 | 0.91 [0.83, 1.00] | 6.40E-06 | 0.87 [0.82, 0.92] |
| rs1335510 | G | 0.41 | 1.14E-04 | 0.84 [0.77, 0.92] | - | - | - | - |
| rs935053* | A | 0.49 | 4.72E-06 | 0.81 [0.74, 0.89] | - | - | - | - |
| rs10757257 | A | 0.41 | 3.39E-05 | 0.83 [0.76, 0.91] | - | - | - | - |
| rs7023329 | G | 0.50 | 1.14E-05 | 0.82 [0.75, 0.90] | 0.023 | 0.90 [0.82, 0.99] | 4.03E-07 | 0.85 [0.80, 0.91] |
|
Chromosome 11: 88551344-88667691 |
||||||||
| rs1042602 (A) | A | 0.39 | 1.13E-01 | 0.93 [0.85, 1.02] | 0.054 | 0.91 [0.83, 1.00] | 1.07E-02 | 0.92 [0.87, 0.98] |
| rs1393350 | A | 0.27 | 4.28E-08 | 1.30 [1.19, 1.43] | 1.38E-07 | 1.30 [1.18, 1.44] | 2.41E-14 | 1.29 [1.21, 1.38] |
| rs1126809 (B) | A | 0.27 | - | - | 1.17E-06 | 1.27 [1.16, 1.40] | 1.17E-06 | 1.27 [1.16, 1.40] |
| rs1847142 (C )* | A | 0.32 | 8.35E-09 | 1.33 [1.21, 1.47] | 6.48E-04 | 1.26 [1.10, 1.44] | 2.24E-11 | 1.31 [1.21, 1.41] |
| rs1806319 | C | 0.35 | 2.49E-06 | 1.24 [1.13, 1.35] | - | - | - | - |
| rs10830253 (D) | G | 0.31 | - | - | 2.81E-06 | 1.26 [1.14, 1.39] | 2.81E-06 | 1.26 [1.14, 1.39] |
|
Chromosome 16: 87913062-88607035 |
||||||||
| rs2353033 | C | 0.41 | 3.32E-07 | 1.26 [1.15, 1.38] | - | - | - | - |
| rs352935 | C | 0.46 | 5.78E-06 | 1.22 [1.12. 1.33] | - | - | - | - |
| rs164741 | A | 0.29 | 1.50E-06 | 1.26 [1.15, 1.39] | - | - | - | - |
| rs7188458 (E) | A | 0.42 | 7.99E-11 | 1 34 [1.23, 1.46] | 1.20E-03 | 1.25 [1.09, 1.42] | 1.16E-12 | 1.30 [1.21, 1.40] |
| rs459920 | C | 0.47 | 5.41E-06 | 0.82 [0.75, 0.89] | - | - | - | - |
| rs12918773* | A | 0.08 | 1.34E-16 | 1.87 [1.62, 2.16] | - | - | - | - |
| rs258322 | A | 0.09 | 7.54E-17 | 1.81 [1.58, 2.08] | 1.07E-10 | 1.55 [1.36, 1,77] | 2.54E-27 | 1.67 [1.52, 1.83] |
| rs1800359 | A | 0.42 | 1.41E-06 | 0.80 [0.74, 0.88] | - | - | - | - |
| rs11861084 | A | 0.43 | 1.64E-06 | 0.81 [0.74, 0.88] | - | - | - | - |
| rs4408545 | T | 0.51 | 1.29E-06 | 0.81 [0.74, 0.88] | - | - | - | - |
| rs4238833 | G | 0.36 | 1.04E-09 | 1.32 [1.21, 1.44] | - | - | - | - |
| rs4785763 | A | 0.32 | 2.84E-14 | 1.42 [1.30, 1.56] | 5.13E-08 | 1.30 [1.18, 1.43] | 5.96E-22 | 1.36 [1.28, 1.45] |
| rs8059973 | A | 0.17 | 6.81E-07 | 0.74 [0.65, 0.83) | - | - | - | - |
| Chromosomal Regions Considered for Followup on Basis of Other Studies | ||||||||
|
Chromosome 20: 32635433-33040650 |
||||||||
| rs910873 | A | 0.07 | - | - | 1.92E-08 | 1.55 [1.33, 1.81] | 1.92E-08 | 1.55 [1.33, 1.81] |
| rs17305573 | C | 0.09 | - | - | 3.95E-05 | 1.53 [1.25, 1.87] | 395E-05 | 1.53 [1.25, 1.87] |
| rs4911442 | G | 0.12 | - | - | 1.80E-05 | 1.48 [1.24, 1,77] | 1.80E-05 | 1.48 [1,24, 1.77] |
| rs1885120 | C | 0.07 | - | - | 1.25E-08 | 1.58 [1.35, 1.85] | 1.25E-08 | 1.58 [1.35, 1.85] |
|
Chromsome 22: 36874244-36875565 |
||||||||
| rs2284063 | G | 0.37 | 5.60E-05 | 0.83 [0.76, 0.91] | 6.45E-05 | 0.82 [0.75, 0.90] | 2.40E-09 | 0.83 [0.78, 0.88] |
| rs6001027 | G | 0.37 | 4.50E-05 | 0.83 [0.76, 0.91] | 2.26E-03 | 0.86 [0.78, 0.95] | 1.94E-08 | 0.83 [0.78, 0.89] |
P-values and ORs (stratified by geographic region) are given for the genome-wide data, the replication data and the two stages combined. Imputed SNPs are marked with an asterisk (*) after the SNP number. Other SNPs are genotyped in the genome-wide dataset. The replication data sets consist of the Leeds case-control study and GenoMEL case-control samples. The following SNPs were also examined because of published literature: (A) rs1042602 was reported to be associated with hair colour and skin phenotype, so was genotyped in both replication sets11, (B) rs1126809 is a functional SNP in TYR, so was genotyped in both replication sets. Also, (C) rsl87142 was genotyped in the genome-wide dataset and in the Leeds case-control samples but not genotyped in the GenoMEL replication set, (D) rsl0830253 is a replacement for rsl806319 and (E) rs7188458 was genotyped in the genome-wide dataset and in the GenoMEL replication set but was not genotyped in the Leeds case-control samples. The table also includes two other regions implicated to contain melanoma susceptibility genes. The chromosome 20 region contains ASIP, a pigmentation gene, identified by an analysis of pigmentation genes11 which is in proximity to a region identified in a pooled genome-wide analysis21 (none of these SNPs were on the genome-wide array); the chromosome 22 region was identified in an adjoining paper involving a GWAS of nevus count variation22.