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


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.

SUBMITTER: Barrett JH 

PROVIDER: S-EPMC3251256 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Barrett Jennifer H JH   Iles Mark M MM   Harland Mark M   Taylor John C JC   Aitken Joanne F JF   Andresen Per Arne PA   Akslen Lars A LA   Armstrong Bruce K BK   Avril Marie-Francoise MF   Azizi Esther E   Bakker Bert B   Bergman Wilma W   Bianchi-Scarrà Giovanna G   Bressac-de Paillerets Brigitte B   Calista Donato D   Cannon-Albright Lisa A LA   Corda Eve E   Cust Anne E AE   Dębniak Tadeusz T   Duffy David D   Dunning Alison M AM   Easton Douglas F DF   Friedman Eitan E   Galan Pilar P   Ghiorzo Paola P   Giles Graham G GG   Hansson Johan J   Hocevar Marko M   Höiom Veronica V   Hopper John L JL   Ingvar Christian C   Janssen Bart B   Jenkins Mark A MA   Jönsson Göran G   Kefford Richard F RF   Landi Giorgio G   Landi Maria Teresa MT   Lang Julie J   Lubiński Jan J   Mackie Rona R   Malvehy Josep J   Martin Nicholas G NG   Molven Anders A   Montgomery Grant W GW   van Nieuwpoort Frans A FA   Novakovic Srdjan S   Olsson Håkan H   Pastorino Lorenza L   Puig Susana S   Puig-Butille Joan Anton JA   Randerson-Moor Juliette J   Snowden Helen H   Tuominen Rainer R   Van Belle Patricia P   van der Stoep Nienke N   Whiteman David C DC   Zelenika Diana D   Han Jiali J   Fang Shenying S   Lee Jeffrey E JE   Wei Qingyi Q   Lathrop G Mark GM   Gillanders Elizabeth M EM   Brown Kevin M KM   Goldstein Alisa M AM   Kanetsky Peter A PA   Mann Graham J GJ   Macgregor Stuart S   Elder David E DE   Amos Christopher I CI   Hayward Nicholas K NK   Gruis Nelleke A NA   Demenais Florence F   Bishop Julia A Newton JA   Bishop D Timothy DT  

Nature genetics 20111009 11


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  ...[more]

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