Genome-wide association study identifies three loci associated with melanoma risk

D. Timothy Bishop; Florence Demenais; Mark M. Iles; Mark Harland; John C. Taylor; Eve Corda; Juliette Randerson-Moor; Joanne F. Aitken; Marie Francoise Avril; Esther Azizi; Bert Bakker; Giovanna Bianchi-Scarr; Brigitte Bressac-De Paillerets; Donato Calista; Lisa A. Cannon-Albright; Thomas Chin-A-Woeng; Tadeusz Dbniak; Gilli Galore-Haskel; Paola Ghiorzo; Ivo Gut; Johan Hansson; Marko Hočevar; Veronica Höiom; John L. Hopper; Christian Ingvar; Peter A. Kanetsky; Richard F. Kefford; Maria Teresa Landi; Julie Lang; Jan Lubiski; Rona MacKie; Josep Malvehy; Graham J. Mann; Nicholas G. Martin; Grant W. Montgomery; Frans A. Van Nieuwpoort; Srdjan Novakovic; Håkan Olsson; Susana Puig; Marjan Weiss; Wilbert Van Workum; Diana Zelenika; Kevin M. Brown; Alisa M. Goldstein; Elizabeth M. Gillanders; Anne Boland; Pilar Galan; David E. Elder; Nelleke A. Gruis; Nicholas K. Hayward; G. Mark Lathrop; Jennifer H. Barrett; Julia A. Newton Bishop

doi:10.1038/ng.411

Genome-wide association study identifies three loci associated with melanoma risk

D. Timothy Bishop, Florence Demenais, Mark M. Iles, Mark Harland, John C. Taylor, Eve Corda, Juliette Randerson-Moor, Joanne F. Aitken, Marie Francoise Avril, Esther Azizi, Bert Bakker, Giovanna Bianchi-Scarr, Brigitte Bressac-De Paillerets, Donato Calista, Lisa A. Cannon-Albright, Thomas Chin-A-Woeng, Tadeusz Dbniak, Gilli Galore-Haskel, Paola Ghiorzo, Ivo GutJohan Hansson, Marko Hočevar, Veronica Höiom, John L. Hopper, Christian Ingvar, Peter A. Kanetsky, Richard F. Kefford, Maria Teresa Landi, Julie Lang, Jan Lubiski, Rona MacKie, Josep Malvehy, Graham J. Mann, Nicholas G. Martin, Grant W. Montgomery, Frans A. Van Nieuwpoort, Srdjan Novakovic, Håkan Olsson, Susana Puig, Marjan Weiss, Wilbert Van Workum, Diana Zelenika, Kevin M. Brown, Alisa M. Goldstein, Elizabeth M. Gillanders, Anne Boland, Pilar Galan, David E. Elder, Nelleke A. Gruis, Nicholas K. Hayward, G. Mark Lathrop, Jennifer H. Barrett, Julia A. Newton Bishop

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

Abstract

We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P <5 × 10 ^-7. Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 × 10 ²⁷ for rs258322), 11q14-q21 encompassing TYR (P = 2.41 × 10 ¹⁴ for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 × 10 ⁷ for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.

Original language	English
Pages (from-to)	920-925
Number of pages	6
Journal	Nature Genetics
Volume	41
Issue number	8
DOIs	https://doi.org/10.1038/ng.411
State	Published - Aug 2009

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Bishop, D. T., Demenais, F., Iles, M. M., Harland, M., Taylor, J. C., Corda, E., Randerson-Moor, J., Aitken, J. F., Avril, M. F., Azizi, E., Bakker, B., Bianchi-Scarr, G., Bressac-De Paillerets, B., Calista, D., Cannon-Albright, L. A., Chin-A-Woeng, T., Dbniak, T., Galore-Haskel, G., Ghiorzo, P., ... Newton Bishop, J. A. (2009). Genome-wide association study identifies three loci associated with melanoma risk. Nature Genetics, 41(8), 920-925. https://doi.org/10.1038/ng.411

@article{ac22c5e4987145639bb2e0db1848f176,

title = "Genome-wide association study identifies three loci associated with melanoma risk",

abstract = "We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P <5 × 10 -7. Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 × 10 27 for rs258322), 11q14-q21 encompassing TYR (P = 2.41 × 10 14 for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 × 10 7 for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.",

author = "Bishop, {D. Timothy} and Florence Demenais and Iles, {Mark M.} and Mark Harland and Taylor, {John C.} and Eve Corda and Juliette Randerson-Moor and Aitken, {Joanne F.} and Avril, {Marie Francoise} and Esther Azizi and Bert Bakker and Giovanna Bianchi-Scarr and {Bressac-De Paillerets}, Brigitte and Donato Calista and Cannon-Albright, {Lisa A.} and Thomas Chin-A-Woeng and Tadeusz Dbniak and Gilli Galore-Haskel and Paola Ghiorzo and Ivo Gut and Johan Hansson and Marko Ho{\v c}evar and Veronica H{\"o}iom and Hopper, {John L.} and Christian Ingvar and Kanetsky, {Peter A.} and Kefford, {Richard F.} and Landi, {Maria Teresa} and Julie Lang and Jan Lubiski and Rona MacKie and Josep Malvehy and Mann, {Graham J.} and Martin, {Nicholas G.} and Montgomery, {Grant W.} and {Van Nieuwpoort}, {Frans A.} and Srdjan Novakovic and H{\aa}kan Olsson and Susana Puig and Marjan Weiss and {Van Workum}, Wilbert and Diana Zelenika and Brown, {Kevin M.} and Goldstein, {Alisa M.} and Gillanders, {Elizabeth M.} and Anne Boland and Pilar Galan and Elder, {David E.} and Gruis, {Nelleke A.} and Hayward, {Nicholas K.} and Lathrop, {G. Mark} and Barrett, {Jennifer H.} and {Newton Bishop}, {Julia A.}",

note = "Funding Information: The study was funded by the European Commission under the 6th Framework Programme, contract no: LSHC-CT-2006-018702, by Cancer Research UK Programme Award (C588/A4994) and by US National Institutes of Health R01 ROI CA83115. Work at CNG was supported by the Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur et de la Recherche and Institut National du Cancer (INCa). Funding Information: This study was also supported by the following: research grant no. C-20070050 from the Israel Cancer Association, the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and by National Cancer Institute grants RO1 CA5558 to M.T.L. Grants 03/0019 and 06/ 0265 from Fondo de Investigaciones Sanitarias; grant RO-1 CA 83115 (fund 538226 from National Cancer Institute); Francisco Cuellar from CONACYT, Mexico, 2007 Italian Ministry of Health DGRST.4/4235-P1.9.A.B to G.B.-S., the Swedish Cancer Society, Kamprad Foundation, Lund Hospital Fund, National Institutes of Health (#CA88363), The Swedish Cancer Society (Grant No: 4860-B06-04XBC), The Swedish Research Council (Grant No: K2006-74X-20141-01-3) and the Radiumhemmet Research Funds. Grants from Institut National du Cancer (INCa-PL016) and Ligue Nationale contre le Cancer (PRE2005.LNCC/FD) to F.D., PHRC2007 (AOM-07-195) to M.-F.A. and F.D., grant from Institut National du Cancer (Melanoma Network RS Number 13) to B.B.-deP. This work was developed in the Melanoma Unit of Hospital Clinic I Provincial de Barcelona, IDIBAPS. Ascertainment and data collection in Sydney and the Australian Melanoma Family Study (AMFS) was supported by NHMRC grants 107359, 200071 and 402761 and grants from Cancer Councils of NSW, Victoria and Queensland and the Cancer Institute NSW. J.H. is an Australia Fellow of the NHMRC. This work was supported by the Intramural Program at the National Human Genome Research Institute, National Institutes of Health. Funding was provided by NIH National Cancer Institute grant RO1 CA102422 (to L.A.C.-A.). The Principal Investigators of Q-MEGA would like to thank D. Statham, M. de Nooyer, I. Gardner and B. Haddon for project management; A. Henders, M. Campbell and M. Stark for managing sample processing and preparation; D. Smyth and H. Beeby for data management and J. Palmer and J. Simmons for ascertainment of clinical records. We also thank the numerous interviewers who collected questionnaire data. Most of all we thank the individuals with melanoma and their families for their cooperation. Funding Information: The Sydney and AMFS investigators are grateful to all members of the recruitment, data collection and laboratory team, especially C. Watts, R. Dalziell, K. Mahendran, G. St. George and C. Agha-Hamilton and AMFS coordinators J. Maskiell, M. Ferguson and J. Jettan. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data are available from the Wellcome Trust website. Funding for the project was provided by the Wellcome Trust under award 076113.",

year = "2009",

month = aug,

doi = "10.1038/ng.411",

language = "אנגלית",

volume = "41",

pages = "920--925",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "8",

}

Bishop, DT, Demenais, F, Iles, MM, Harland, M, Taylor, JC, Corda, E, Randerson-Moor, J, Aitken, JF, Avril, MF, Azizi, E, Bakker, B, Bianchi-Scarr, G, Bressac-De Paillerets, B, Calista, D, Cannon-Albright, LA, Chin-A-Woeng, T, Dbniak, T, Galore-Haskel, G, Ghiorzo, P, Gut, I, Hansson, J, Hočevar, M, Höiom, V, Hopper, JL, Ingvar, C, Kanetsky, PA, Kefford, RF, Landi, MT, Lang, J, Lubiski, J, MacKie, R, Malvehy, J, Mann, GJ, Martin, NG, Montgomery, GW, Van Nieuwpoort, FA, Novakovic, S, Olsson, H, Puig, S, Weiss, M, Van Workum, W, Zelenika, D, Brown, KM, Goldstein, AM, Gillanders, EM, Boland, A, Galan, P, Elder, DE, Gruis, NA, Hayward, NK, Lathrop, GM, Barrett, JH & Newton Bishop, JA 2009, 'Genome-wide association study identifies three loci associated with melanoma risk', Nature Genetics, vol. 41, no. 8, pp. 920-925. https://doi.org/10.1038/ng.411

TY - JOUR

T1 - Genome-wide association study identifies three loci associated with melanoma risk

AU - Bishop, D. Timothy

AU - Demenais, Florence

AU - Iles, Mark M.

AU - Harland, Mark

AU - Taylor, John C.

AU - Corda, Eve

AU - Randerson-Moor, Juliette

AU - Aitken, Joanne F.

AU - Avril, Marie Francoise

AU - Azizi, Esther

AU - Bakker, Bert

AU - Bianchi-Scarr, Giovanna

AU - Bressac-De Paillerets, Brigitte

AU - Calista, Donato

AU - Cannon-Albright, Lisa A.

AU - Chin-A-Woeng, Thomas

AU - Dbniak, Tadeusz

AU - Galore-Haskel, Gilli

AU - Ghiorzo, Paola

AU - Gut, Ivo

AU - Hansson, Johan

AU - Hočevar, Marko

AU - Höiom, Veronica

AU - Hopper, John L.

AU - Ingvar, Christian

AU - Kanetsky, Peter A.

AU - Kefford, Richard F.

AU - Landi, Maria Teresa

AU - Lang, Julie

AU - Lubiski, Jan

AU - MacKie, Rona

AU - Malvehy, Josep

AU - Mann, Graham J.

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Van Nieuwpoort, Frans A.

AU - Novakovic, Srdjan

AU - Olsson, Håkan

AU - Puig, Susana

AU - Weiss, Marjan

AU - Van Workum, Wilbert

AU - Zelenika, Diana

AU - Brown, Kevin M.

AU - Goldstein, Alisa M.

AU - Gillanders, Elizabeth M.

AU - Boland, Anne

AU - Galan, Pilar

AU - Elder, David E.

AU - Gruis, Nelleke A.

AU - Hayward, Nicholas K.

AU - Lathrop, G. Mark

AU - Barrett, Jennifer H.

AU - Newton Bishop, Julia A.

N1 - Funding Information: The study was funded by the European Commission under the 6th Framework Programme, contract no: LSHC-CT-2006-018702, by Cancer Research UK Programme Award (C588/A4994) and by US National Institutes of Health R01 ROI CA83115. Work at CNG was supported by the Ministère de l’Enseignement Supérieur et de la Recherche and Institut National du Cancer (INCa). Funding Information: This study was also supported by the following: research grant no. C-20070050 from the Israel Cancer Association, the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and by National Cancer Institute grants RO1 CA5558 to M.T.L. Grants 03/0019 and 06/ 0265 from Fondo de Investigaciones Sanitarias; grant RO-1 CA 83115 (fund 538226 from National Cancer Institute); Francisco Cuellar from CONACYT, Mexico, 2007 Italian Ministry of Health DGRST.4/4235-P1.9.A.B to G.B.-S., the Swedish Cancer Society, Kamprad Foundation, Lund Hospital Fund, National Institutes of Health (#CA88363), The Swedish Cancer Society (Grant No: 4860-B06-04XBC), The Swedish Research Council (Grant No: K2006-74X-20141-01-3) and the Radiumhemmet Research Funds. Grants from Institut National du Cancer (INCa-PL016) and Ligue Nationale contre le Cancer (PRE2005.LNCC/FD) to F.D., PHRC2007 (AOM-07-195) to M.-F.A. and F.D., grant from Institut National du Cancer (Melanoma Network RS Number 13) to B.B.-deP. This work was developed in the Melanoma Unit of Hospital Clinic I Provincial de Barcelona, IDIBAPS. Ascertainment and data collection in Sydney and the Australian Melanoma Family Study (AMFS) was supported by NHMRC grants 107359, 200071 and 402761 and grants from Cancer Councils of NSW, Victoria and Queensland and the Cancer Institute NSW. J.H. is an Australia Fellow of the NHMRC. This work was supported by the Intramural Program at the National Human Genome Research Institute, National Institutes of Health. Funding was provided by NIH National Cancer Institute grant RO1 CA102422 (to L.A.C.-A.). The Principal Investigators of Q-MEGA would like to thank D. Statham, M. de Nooyer, I. Gardner and B. Haddon for project management; A. Henders, M. Campbell and M. Stark for managing sample processing and preparation; D. Smyth and H. Beeby for data management and J. Palmer and J. Simmons for ascertainment of clinical records. We also thank the numerous interviewers who collected questionnaire data. Most of all we thank the individuals with melanoma and their families for their cooperation. Funding Information: The Sydney and AMFS investigators are grateful to all members of the recruitment, data collection and laboratory team, especially C. Watts, R. Dalziell, K. Mahendran, G. St. George and C. Agha-Hamilton and AMFS coordinators J. Maskiell, M. Ferguson and J. Jettan. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data are available from the Wellcome Trust website. Funding for the project was provided by the Wellcome Trust under award 076113.

PY - 2009/8

Y1 - 2009/8

N2 - We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P <5 × 10 -7. Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 × 10 27 for rs258322), 11q14-q21 encompassing TYR (P = 2.41 × 10 14 for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 × 10 7 for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.

AB - We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P <5 × 10 -7. Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 × 10 27 for rs258322), 11q14-q21 encompassing TYR (P = 2.41 × 10 14 for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 × 10 7 for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.

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U2 - 10.1038/ng.411

DO - 10.1038/ng.411

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AN - SCOPUS:68149179663

SN - 1061-4036

VL - 41

SP - 920

EP - 925

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Genome-wide association study identifies three loci associated with melanoma risk

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