Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Leeds Cancer Research UK Centre, St James’s University Hospital, Leeds, UK.
Nat Genet. 2011 Oct 9;43(11):1108-13. doi: 10.1038/ng.959.
We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
我们报告了由 GenoMEL 联盟进行的一项针对黑色素瘤的全基因组关联研究。我们的发现阶段包括 2981 名黑色素瘤患者和 1982 名具有欧洲血统的特定研究对照个体，以及来自法国或英国人群的另外 6426 名对照个体，所有这些个体均针对 317000 个或 610000 个单核苷酸多态性 (SNP) 进行了基因分型。我们的分析复制了先前已知的黑色素瘤易感位点。选择了七个具有至少一个 P < 10(-5) SNP 且进一步具有局部推断或基因分型支持的新区域，用于使用另外两个全基因组研究（来自澳大利亚和美国得克萨斯州）进行复制。来自英国和荷兰的病例对照系列也提供了额外的复制。七个位点中的三个在 P < 10(-3) 时复制：ATM 中的 SNP(rs1801516，总 P = 3.4 × 10(-9))、MX2 中的 SNP(rs45430，P = 2.9 × 10(-9)) 和 CASP8 附近的 SNP(rs13016963，P = 8.6 × 10(-10))。靠近 CCND1 的第四个位点仍然具有潜在的研究意义，显示出复制的暗示但不明确的证据(rs1485993，在固定效应模型下总 P = 4.6 × 10(-7)，在随机效应模型下 P = 1.2 × 10(-3))。在一个大型英国病例对照系列中，这些新关联的变体与痣或色素沉着表型没有关联。
