Genome-wide association study identifies three new melanoma susceptibility loci

JH Barrett, MM Iles, M Harland, JC Taylor, JF Aitken… - Nature …, 2011 - nature.com
JH Barrett, MM Iles, M Harland, JC Taylor, JF Aitken, PA Andresen, LA Akslen, BK Armstrong…
Nature genetics, 2011nature.com
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 …
Abstract
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.
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