A variant in FTO shows association with melanoma risk not due to BMI

Mark M. Iles; Matthew H. Law; Simon N. Stacey; Jiali Han; Shenying Fang; Ruth Pfeiffer; Mark Harland; Stuart MacGregor; John C. Taylor; Katja K. Aben; Lars A. Akslen; Marie Françoise Avril; Esther Azizi; Bert Bakker; Kristrun R. Benediktsdottir; Wilma Bergman; Giovanna Bianchi Scarrà; Kevin M. Brown; Donato Calista; Valérie Chaudru; Maria Concetta Fargnoli; Anne E. Cust; Florence Demenais; Anne C. De Waal; Tadeusz Dȩbniak; David E. Elder; Eitan Friedman; Pilar Galan; Paola Ghiorzo; Elizabeth M. Gillanders; Alisa M. Goldstein; Nelleke A. Gruis; Johan Hansson; Per Helsing; Marko Hočevar; Veronica Höiom; John L. Hopper; Christian Ingvar; Marjolein Janssen; Mark A. Jenkins; Peter A. Kanetsky; Lambertus A. Kiemeney; Julie Lang; G. Mark Lathrop; Sancy Leachman; Jeffrey E. Lee; Jan Lubiński; Rona M. MacKie; Graham J. Mann; Nicholas G. Martin; Jose I. Mayordomo; Anders Molven; Suzanne Mulder; Eduardo Nagore; Srdjan Novaković; Ichiro Okamoto; Jon H. Olafsson; Håkan Olsson; Hubert Pehamberger; Ketty Peris; Maria Pilar Grasa; Dolores Planelles; Susana Puig; Joan Anton Puig-Butille; Juliette Randerson-Moor; Celia Requena; Licia Rivoltini; Monica Rodolfo; Mario Santinami; Bardur Sigurgeirsson; Helen Snowden; Fengju Song; Patrick Sulem; Kristin Thorisdottir; Rainer Tuominen; Patricia Van Belle; Nienke Van Der Stoep; Michelle M. Van Rossum; Qingyi Wei; Judith Wendt; Diana Zelenika; Mingfeng Zhang; Maria Teresa Landi; Gudmar Thorleifsson; D. Timothy Bishop; Christopher I. Amos; Nicholas K. Hayward; Kari Stefansson; Julia A.Newton Bishop; Jennifer H. Barrett

doi:10.1038/ng.2571

A variant in FTO shows association with melanoma risk not due to BMI

Mark M. Iles^*
, Matthew H. Law
, Simon N. Stacey
, Jiali Han
, Shenying Fang
, Ruth Pfeiffer
, Mark Harland
, Stuart MacGregor
, John C. Taylor
, Katja K. Aben
, Lars A. Akslen
, Marie Françoise Avril
, Esther Azizi
, Bert Bakker
, Kristrun R. Benediktsdottir
, Wilma Bergman
, Giovanna Bianchi Scarrà
, Kevin M. Brown
, Donato Calista
, Valérie Chaudru

Maria Concetta Fargnoli, Anne E. Cust, Florence Demenais, Anne C. De Waal, Tadeusz Dȩbniak, David E. Elder, Eitan Friedman, Pilar Galan, Paola Ghiorzo, Elizabeth M. Gillanders, Alisa M. Goldstein, Nelleke A. Gruis, Johan Hansson, Per Helsing, Marko Hočevar, Veronica Höiom, John L. Hopper, Christian Ingvar, Marjolein Janssen, Mark A. Jenkins, Peter A. Kanetsky, Lambertus A. Kiemeney, Julie Lang, G. Mark Lathrop, Sancy Leachman, Jeffrey E. Lee, Jan Lubiński, Rona M. MacKie, Graham J. Mann, Nicholas G. Martin, Jose I. Mayordomo, Anders Molven, Suzanne Mulder, Eduardo Nagore, Srdjan Novaković, Ichiro Okamoto, Jon H. Olafsson, Håkan Olsson, Hubert Pehamberger, Ketty Peris, Maria Pilar Grasa, Dolores Planelles, Susana Puig, Joan Anton Puig-Butille, Juliette Randerson-Moor, Celia Requena, Licia Rivoltini, Monica Rodolfo, Mario Santinami, Bardur Sigurgeirsson, Helen Snowden, Fengju Song, Patrick Sulem, Kristin Thorisdottir, Rainer Tuominen, Patricia Van Belle, Nienke Van Der Stoep, Michelle M. Van Rossum, Qingyi Wei, Judith Wendt, Diana Zelenika, Mingfeng Zhang, Maria Teresa Landi, Gudmar Thorleifsson, D. Timothy Bishop, Christopher I. Amos, Nicholas K. Hayward, Kari Stefansson, Julia A.Newton Bishop, Jennifer H. Barrett

^*Corresponding author for this work

Clinical Departments

Leeds Teaching Hospitals NHS Trust
Queensland Institute of Medical Research
deCODE Genetics
Brigham and Women’s Hospital
Harvard University
University of Texas MD Anderson Cancer Center
National Institutes of Health
Netherlands Association of Comprehensive Cancer Centres
Radboud University Nijmegen
University of Bergen
Université Paris Cité
Leiden University
University of Iceland
Landspitali University Hospital
University of Genoa
University and San Martino Hospital of Genoa
Ospedale M. Bufalini
Institut national de la santé et de la recherche médicale
Université d'Evry
Centre d'Etude du Polymorphisme Humain
University of L'Aquila
The University of Sydney
Sorbonne Paris Cité (CRESS)
Pomeranian Medical University in Szczecin
University of Pennsylvania
University of Paris 13
Karolinska Institutet
University of Oslo
Institute of Oncology Ljubljana
University of Melbourne
Lund University
ServiceXS B.V.
University of Glasgow
Commissariat à l'Energie Atomique, Institut de Génomique, Centre National de Génotypage
University of Utah
University of Zaragoza
Instituto Valenciano de Oncologia
Medical University of Vienna
Center for Blood Transfusion
University of Barcelona
Instituto de Salud Carlos III
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
Tianjin Medical University
Dartmouth College

Research output: Contribution to journal › Article › peer-review

110 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	428-432
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	4
DOIs	https://doi.org/10.1038/ng.2571
State	Published - Apr 2013

Funding

Funders	Funder number
ERC-2011-AdG 294576-risk factors cancer
Cancer Councils New South Wales, Victoria and Queensland
Instituto de Salud Carlos III
Dutch Cancer Society Koningin Wilhemina Fonds
Institut de Génomique–Commissariat à l’Energie Atomique
Cerylid Biosciences
Cancerfonden
Northern Ireland Community Relations Council
Hans und Blanca Moser Stiftung
European Commission
Radboud Universitair Medisch Centrum
Australian Cancer Research Foundation
Ministère de l'Enseignement Supérieur et de la Recherche
Karolinska Institutet
Institut National du Cancer
KWF Kankerbestrijding
Catalan Government, Spain
Division of Cancer Epidemiology and Genetics, National Cancer Institute
Cooperative Research Centre for Discovery of Genes for Common Human Diseases
Centro de Investigaciones Biomedicas en Red
Cancer Institute NSW
U.S. Department of Health and Human Services
Gunnar Nilsson Foundation
Marit Peterson Fund for Melanoma Research
European Research Council
National Health and Medical Research Council	389927,389875, 389892, 389892,389938, 389891, 552485, 241944, 443036, 442981, 552498, 496739, 200071, 380385, 496674, 496675, 442915, 496610
Wellcome Trust	613705, WT084766/Z/08/Z, 076113, 084766
Seventh Framework Programme	339462, 294576
Melanoma Research Alliance	CA055075
National Institutes of Health	CA65558-02
National Cancer Institute	ZIACP004410, P30CA023108, R01CA083115, R01CA122838, R01CA092824, R01CA065558, R01CA088363, R01CA100264, P01CA087969, P30CA016520, R01CA133996, R01CA049449, P50CA093459
Ministero dell’Istruzione, dell’Università e della Ricerca	2008W8JTPA_002
Programme Hospitalier de Recherche Clinique	AOM-07-195
NIH NCI	P30CA023108, 2P50CA093459
Agència de Gestió d'Ajuts Universitaris i de Recerca	SGR-1337
Leeds Cancer Research UK Centre	C37059/A11941
Sixth Framework Programme	LSHC-CT-2006-018702
Cancer Australia	1011143
Ligue Contre le Cancer	PRE05/ FD
Oesterreichische Nationalbank	12161, 13036
Cancer Research UK	C588/A10589, C8216/A6129, C588/A4994
Intergruppo Melanoma Italiano and Mara Naum foundation	INCa-PL016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1038/ng.2571

Cite this

Iles, M. M., Law, M. H., Stacey, S. N., Han, J., Fang, S., Pfeiffer, R., Harland, M., MacGregor, S., Taylor, J. C., Aben, K. K., Akslen, L. A., Avril, M. F., Azizi, E., Bakker, B., Benediktsdottir, K. R., Bergman, W., Scarrà, G. B., Brown, K. M., Calista, D., ... Barrett, J. H. (2013). A variant in FTO shows association with melanoma risk not due to BMI. Nature Genetics, 45(4), 428-432. https://doi.org/10.1038/ng.2571

@article{5d34fa08ee554e519a45584483fdad90,

title = "A variant in FTO shows association with melanoma risk not due to BMI",

abstract = "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.",

author = "Iles, \{Mark M.\} and Law, \{Matthew H.\} and Stacey, \{Simon N.\} and Jiali Han and Shenying Fang and Ruth Pfeiffer and Mark Harland and Stuart MacGregor and Taylor, \{John C.\} and Aben, \{Katja K.\} and Akslen, \{Lars A.\} and Avril, \{Marie Fran{\c c}oise\} and Esther Azizi and Bert Bakker and Benediktsdottir, \{Kristrun R.\} and Wilma Bergman and Scarr{\`a}, \{Giovanna Bianchi\} and Brown, \{Kevin M.\} and Donato Calista and Val{\'e}rie Chaudru and Fargnoli, \{Maria Concetta\} and Cust, \{Anne E.\} and Florence Demenais and \{De Waal\}, \{Anne C.\} and Tadeusz Dȩbniak and Elder, \{David E.\} and Eitan Friedman and Pilar Galan and Paola Ghiorzo and Gillanders, \{Elizabeth M.\} and Goldstein, \{Alisa M.\} and Gruis, \{Nelleke A.\} and Johan Hansson and Per Helsing and Marko Ho{\v c}evar and Veronica H{\"o}iom and Hopper, \{John L.\} and Christian Ingvar and Marjolein Janssen and Jenkins, \{Mark A.\} and Kanetsky, \{Peter A.\} and Kiemeney, \{Lambertus A.\} and Julie Lang and Lathrop, \{G. Mark\} and Sancy Leachman and Lee, \{Jeffrey E.\} and Jan Lubi{\'n}ski and MacKie, \{Rona M.\} and Mann, \{Graham J.\} and Martin, \{Nicholas G.\} and Mayordomo, \{Jose I.\} and Anders Molven and Suzanne Mulder and Eduardo Nagore and Srdjan Novakovi{\'c} and Ichiro Okamoto and Olafsson, \{Jon H.\} and H{\aa}kan Olsson and Hubert Pehamberger and Ketty Peris and Grasa, \{Maria Pilar\} and Dolores Planelles and Susana Puig and Puig-Butille, \{Joan Anton\} and Juliette Randerson-Moor and Celia Requena and Licia Rivoltini and Monica Rodolfo and Mario Santinami and Bardur Sigurgeirsson and Helen Snowden and Fengju Song and Patrick Sulem and Kristin Thorisdottir and Rainer Tuominen and \{Van Belle\}, Patricia and \{Van Der Stoep\}, Nienke and \{Van Rossum\}, \{Michelle M.\} and Qingyi Wei and Judith Wendt and Diana Zelenika and Mingfeng Zhang and Landi, \{Maria Teresa\} and Gudmar Thorleifsson and Bishop, \{D. Timothy\} and Amos, \{Christopher I.\} and Hayward, \{Nicholas K.\} and Kari Stefansson and Bishop, \{Julia A.Newton\} and Barrett, \{Jennifer H.\}",

note = "Funding Information: the Comprehensive Cancer Center, Oslo University Hospital (SE0728) and the Norwegian Cancer Society (71512-PR-2006-0356). Work in Vienna was supported by the Jubil{\"a}umsfonds of the {\"O}sterreichische 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. Funding Information: 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 G{\'e}notypage, Institut de G{\'e}nomique–Commissariat {\`a} l{\textquoteright}Energie Atomique and was supported by the Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur 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 Gesti{\'o} d{\textquoteright}Ajuts Universitaris i de Recerca 2009 SGR-1337 of the Catalan Government, Spain. Work in Norway was funded by grants from",

year = "2013",

month = apr,

doi = "10.1038/ng.2571",

language = "אנגלית",

volume = "45",

pages = "428--432",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "4",

}

Iles, MM, Law, MH, Stacey, SN, Han, J, Fang, S, Pfeiffer, R, Harland, M, MacGregor, S, Taylor, JC, Aben, KK, Akslen, LA, Avril, MF, Azizi, E, Bakker, B, Benediktsdottir, KR, Bergman, W, Scarrà, GB, Brown, KM, Calista, D, Chaudru, V, Fargnoli, MC, Cust, AE, Demenais, F, De Waal, AC, Dȩbniak, T, Elder, DE, Friedman, E, Galan, P, Ghiorzo, P, Gillanders, EM, Goldstein, AM, Gruis, NA, Hansson, J, Helsing, P, Hočevar, M, Höiom, V, Hopper, JL, Ingvar, C, Janssen, M, Jenkins, MA, Kanetsky, PA, Kiemeney, LA, Lang, J, Lathrop, GM, Leachman, S, Lee, JE, Lubiński, J, MacKie, RM, Mann, GJ, Martin, NG, Mayordomo, JI, Molven, A, Mulder, S, Nagore, E, Novaković, S, Okamoto, I, Olafsson, JH, Olsson, H, Pehamberger, H, Peris, K, Grasa, MP, Planelles, D, Puig, S, Puig-Butille, JA, Randerson-Moor, J, Requena, C, Rivoltini, L, Rodolfo, M, Santinami, M, Sigurgeirsson, B, Snowden, H, Song, F, Sulem, P, Thorisdottir, K, Tuominen, R, Van Belle, P, Van Der Stoep, N, Van Rossum, MM, Wei, Q, Wendt, J, Zelenika, D, Zhang, M, Landi, MT, Thorleifsson, G, Bishop, DT, Amos, CI, Hayward, NK, Stefansson, K, Bishop, JAN & Barrett, JH 2013, 'A variant in FTO shows association with melanoma risk not due to BMI', Nature Genetics, vol. 45, no. 4, pp. 428-432. https://doi.org/10.1038/ng.2571

TY - JOUR

T1 - A variant in FTO shows association with melanoma risk not due to BMI

AU - Iles, Mark M.

AU - Law, Matthew H.

AU - Stacey, Simon N.

AU - Han, Jiali

AU - Fang, Shenying

AU - Pfeiffer, Ruth

AU - Harland, Mark

AU - MacGregor, Stuart

AU - Taylor, John C.

AU - Aben, Katja K.

AU - Akslen, Lars A.

AU - Avril, Marie Françoise

AU - Azizi, Esther

AU - Bakker, Bert

AU - Benediktsdottir, Kristrun R.

AU - Bergman, Wilma

AU - Scarrà, Giovanna Bianchi

AU - Brown, Kevin M.

AU - Calista, Donato

AU - Chaudru, Valérie

AU - Fargnoli, Maria Concetta

AU - Cust, Anne E.

AU - Demenais, Florence

AU - De Waal, Anne C.

AU - Dȩbniak, Tadeusz

AU - Elder, David E.

AU - Friedman, Eitan

AU - Galan, Pilar

AU - Ghiorzo, Paola

AU - Gillanders, Elizabeth M.

AU - Goldstein, Alisa M.

AU - Gruis, Nelleke A.

AU - Hansson, Johan

AU - Helsing, Per

AU - Hočevar, Marko

AU - Höiom, Veronica

AU - Hopper, John L.

AU - Ingvar, Christian

AU - Janssen, Marjolein

AU - Jenkins, Mark A.

AU - Kanetsky, Peter A.

AU - Kiemeney, Lambertus A.

AU - Lang, Julie

AU - Lathrop, G. Mark

AU - Leachman, Sancy

AU - Lee, Jeffrey E.

AU - Lubiński, Jan

AU - MacKie, Rona M.

AU - Mann, Graham J.

AU - Martin, Nicholas G.

AU - Mayordomo, Jose I.

AU - Molven, Anders

AU - Mulder, Suzanne

AU - Nagore, Eduardo

AU - Novaković, Srdjan

AU - Okamoto, Ichiro

AU - Olafsson, Jon H.

AU - Olsson, Håkan

AU - Pehamberger, Hubert

AU - Peris, Ketty

AU - Grasa, Maria Pilar

AU - Planelles, Dolores

AU - Puig, Susana

AU - Puig-Butille, Joan Anton

AU - Randerson-Moor, Juliette

AU - Requena, Celia

AU - Rivoltini, Licia

AU - Rodolfo, Monica

AU - Santinami, Mario

AU - Sigurgeirsson, Bardur

AU - Snowden, Helen

AU - Song, Fengju

AU - Sulem, Patrick

AU - Thorisdottir, Kristin

AU - Tuominen, Rainer

AU - Van Belle, Patricia

AU - Van Der Stoep, Nienke

AU - Van Rossum, Michelle M.

AU - Wei, Qingyi

AU - Wendt, Judith

AU - Zelenika, Diana

AU - Zhang, Mingfeng

AU - Landi, Maria Teresa

AU - Thorleifsson, Gudmar

AU - Bishop, D. Timothy

AU - Amos, Christopher I.

AU - Hayward, Nicholas K.

AU - Stefansson, Kari

AU - Bishop, Julia A.Newton

AU - Barrett, Jennifer H.

N1 - Funding Information: 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. Funding Information: 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

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84875722359

U2 - 10.1038/ng.2571

DO - 10.1038/ng.2571

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:84875722359

SN - 1061-4036

VL - 45

SP - 428

EP - 432

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

A variant in FTO shows association with melanoma risk not due to BMI

Abstract

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this