Genetic Architecture of Susceptibility to Melanoma

Most genetic susceptibility to cutaneous melanoma (CM) remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 melanoma cases (67% newly-genotyped) and 375,188 controls identified 54 significant loci with 68 independent SNPs. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with nevus count and hair colour GWAS, and transcriptome association approaches, uncovered 31 potential secondary loci, for a total of 85 CM susceptibility loci. These findings provide substantial insights into CM genetic architecture, reinforcing the importance of nevogenesis, pigmentation, and telomere maintenance together with identifying potential new pathways for CM pathogenesis.]]>
We performed a genome-wide association analysis (GWAS) meta-analysis of cutaneous melanoma susceptibility with 30,134 clinically cases and 81415 CM-free controls from the United Kingdom, United States, Australia, Northern and Western Europe as well as the Mediterranean. Samples were genotyped using different SNP array genotyping platforms .