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Nat Genet. 2011 Oct 9;43(11):1108-13. doi: 10.1038/ng.959.

Genome-wide association study identifies three new melanoma susceptibility loci.

Collaborators (205)

Mann GJ, Hopper JL, Aitken JF, Armstrong BK, Giles GG, Kefford RF, Cust A, Jenkins M, Schmid H, Aguilera P, Badenas C, Carrera C, Cuellar F, Gabriel D, Martinez E, Gonzalez M, Iglesias P, Malvehy J, Marti-Laborda R, Mila M, Puig Butille JA, Puig S, Alós L, Arance A, Arguís P, Campo A, Castel T, Conill C, Palou J, Rull R, Sánchez M, Vidal S, Vilalta A, Vilella R, Martin NG, Montgomery GW, Duffy D, Whiteman D, MacGregor S, Hayward NK, Whiteman D, Webb P, Green A, Parsons P, Purdie D, Hayward N, Landi MT, Calista D, Landi G, Minghetti P, Arcangeli F, Bertazzi PA, Bianchi G, Ghiorzo P, Pastorino L, Bruno W, Battistuzzi L, Gargiulo S, Nasti S, Gliori S, Origone P, Andreotti V, Queirolo P, Mackie R, Newton Bishop JA, Affleck P, Barrett JH, Timothy Bishop D, Harrison J, Iles M, Randerson J, Harland M, Taylor C, Whittaker L, Kukalizch K, Leake S, Karpavicius B, Haynes S, Mack T, Chan M, Taylor Y, Davies J, King P, Gruis NA, van Nieuwpoort FA, Out C, van der Drift C, Bergman W, Kukutsch N, Bouwes Bavinck JN, Bakker B, van der Stoep N, Huurne Jt, van der Rhee H, Bekkenk M, Snels D, van Praag M, Brochez L, Gerritsen R, Crijns M, Vasen H, Ingvar C, Jönsson G, Borg Å, Måsbäck A, Lundgren L, Baeckenhorn K, Nielsen K, Schmidt Casslén A, Helsing P, Andresen PA, Rootwelt H, Akslen LA, Molven A, Avril F, Bressac B, Chaudru V, Chateigner N, Corda E, Jeannin P, Lesueur F, de Lichy M, Maubec E, Mohamdi H, Demenais F, Andry P, Bachollet B, Bérard F, Berthet P, Boitier F, Bonadona V, Bonafé L, Bonnetblanc M, Cambazard F, Caron O, Caux F, Chevrant J, Chompret A, Demange L, Dereure O, Doré X, Doutre S, Dugast C, Faivre L, Grange F, Humbert P, Joly P, Kerob D, Lasset C, Thérèse Leccia M, Lenoir G, Leroux D, Levang J, Lipsker D, Mansard S, Martin L, Martin T, Mateus C, Michel L, Morel P, Olivier L, Perrot L, Robert C, Ronger S, Sassolas B, Souteyrand P, Stoppa D, Thomas L, Vabres P, Wierzbicka E, Elder D, Kanetsky P, Knorr J, Ming M, Mitra N, Ruffin A, Van P, Lubiński J, Mirecka A, Novakovic S, Hocevar M, Peric B, Cerkovnik P, Höiom V, Hansson J, Mann GJ, Kefford RF, Schmid H, Holland EA, Azizi E, Galore G, Friedman E, Baron O, Scope A, Pavlotsky F, Yakobson E, Cohen I, Laitman Y, Milgrom R, Shimoni I, Dunning A, Easton D, Margerison L, Pooley K, Smith P.

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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