2 research outputs found
Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma
Thirteen common susceptibility loci have been reproducibly associated
with cutaneous malignant melanoma (CMM). We report the results of an
international 2-stage meta-analysis of CMM genome-wide association
studies (GWAS). This meta-analysis combines 11 GWAS (5 previously
unpublished) and a further three stage 2 data sets, totaling 15,990 CMM
cases and 26,409 controls. Five loci not previously associated with CMM
risk reached genome-wide significance (P < 5 x 10(-8)), as did 2
previously reported but unreplicated loci and all 13 established loci.
Newly associated SNPs fall within putative melanocyte regulatory
elements, and bioinformatic and expression quantitative trait locus
(eQTL) data highlight candidate genes in the associated regions,
including one involved in telomere biology
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. 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 GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis