We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 × 10−12, per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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We thank M.I. McCarthy and C.M. Lindgren for assistance with the results of the GIANT study. The GenoMEL study was funded by the European Commission under the 6th Framework Programme (contract number LSHC-CT-2006-018702), by Cancer Research UK Programme Awards (C588/A4994 and C588/A10589), by a Cancer Research UK Project Grant (C8216/A6129), by the Leeds Cancer Research UK Centre (C37059/A11941) and by a grant from the US National Institutes of Health (NIH; CA83115). This research was also supported by the intramural Research Program of the NIH, US National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics. Genotyping of most of the samples collected in France that were included in GenoMEL was done at Centre National de Génotypage, Institut de Génomique–Commissariat à l'Energie Atomique and was supported by the Ministère de l'Enseignement Supérieur et de la Recherche and Institut National du Cancer (INCa). This study used data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from their website (see URLs); funding for the project was provided by the Wellcome Trust under award 076113. We thank the EGEA cooperative group for giving access to data of the EGEA study (see URLs). We acknowledge that the biological specimens of the French Familial Melanoma Study Group were obtained from the Institut Gustave Roussy and Fondation Jean Dausset–CEPH Biobanks. Work in Stockholm was funded by the Swedish Cancer Society and Karolinska Institutet research funds. Work in Lund was funded by the Swedish Cancer Society, the Gunnar Nilsson Foundation and the European Research Council (ERC-2011-AdG 294576-risk factors cancer). Work in Genoa was funded by the Italian Ministry of Education, University and Research Progetti di Ricerca di Interesse Nazionale (2008W8JTPA_002), Intergruppo Melanoma Italiano and Mara Naum foundation. Work in Paris was funded by grants from INCa (INCa-PL016) and Ligue Nationale Contre Le Cancer (PRE05/FD and PRE 09/FD) to F. Demenais, and Programme Hospitalier de Recherche Clinique (AOM-07-195) to M.-F. Avril and F. Demenais. Work in Leiden was funded by a grant provided by European Biobanking and Biomolecular Resources Research Infrastructure Netherlands hub (CO18). Research at the Melanoma Unit in Barcelona is partially funded by grants from Fondo de Investigaciones Sanitarias P.I. 09/01393, Spain and by the Centro de Investigaciones Biomedicas en Red (CIBER) de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the Agencia de Gestió d'Ajuts Universitaris i de Recerca 2009 SGR-1337 of the Catalan Government, Spain. Work in Norway was funded by grants from the Comprehensive Cancer Center, Oslo University Hospital (SE0728) and the Norwegian Cancer Society (71512-PR-2006-0356). Work in Vienna was supported by the Jubiläumsfonds of the Österreichische Nationalbank (project numbers 12161 and 13036) and the Hans und Blanca Moser Stiftung. The Italian study was partially supported by a NIH RO1 grant CA65558-02 (to M.T. Landi), Department of Health and Human Services and by the Intramural Research Program of NIH, NCI Division of Cancer Epidemiology and Genetics. Work at the MD Anderson Cancer Center was supported by the NIH NCI (P30CA023108 and 2P50CA093459) and by the Marit Peterson Fund for Melanoma Research. A. Cust is supported by fellowships from the Cancer Institute New South Wales and the National Health and Medical Research Council. Work in Nijmegen, The Netherlands, was funded by the Dutch Cancer Society Koningin Wilhemina Fonds (KWF) Kankerbestrijding and by the Radboud University Medical Centre. The Q-MEGA study was supported by the Melanoma Research Alliance, the NIH NCI (CA88363, CA83115, CA122838, CA87969, CA055075, CA100264, CA133996 and CA49449), the National Health and Medical Research Council of Australia (NHMRC) (200071, 241944, 339462, 380385, 389927,389875, 389891, 389892,389938, 443036, 442915, 442981, 496610, 496675, 496739, 552485, 552498), the Cancer Councils New South Wales, Victoria and Queensland, the Cancer Institute New South Wales, the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne), the Australian Cancer Research Foundation, The Wellcome Trust (WT084766/Z/08/Z) and donations from Neville and Shirley Hawkins. N.K.H. was supported by the NHMRC Fellowships scheme. SM was supported by a Career Development award from the NHMRC (496674, 613705). M.H.L. is supported by Cancer Australia grant 1011143.
Supplementary Tables 1–2, Supplementary Figures 1–7, Supplementary Note