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 ChaudruMaria 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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)428-432
Number of pages5
JournalNature Genetics
Volume45
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

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Melanoma
Body Mass Index
Single Nucleotide Polymorphism
Introns
Alleles
Obesity
Odds Ratio
Genotype
Genome
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Iles, M. M., Law, M. H., Stacey, S. N., Han, J., Fang, S., Pfeiffer, R., ... 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

A variant in FTO shows association with melanoma risk not due to BMI. / Iles, Mark M.; Law, Matthew H.; Stacey, Simon N.; Han, Jiali; Fang, Shenying; Pfeiffer, Ruth; Harland, Mark; MacGregor, Stuart; Taylor, John C.; Aben, Katja K.; Akslen, Lars A.; Avril, Marie Françoise; Azizi, Esther; Bakker, Bert; Benediktsdottir, Kristrun R.; Bergman, Wilma; Scarrà, Giovanna Bianchi; Brown, Kevin M.; Calista, Donato; Chaudru, Valérie; Fargnoli, Maria Concetta; Cust, Anne E.; Demenais, Florence; De Waal, Anne C.; Dȩbniak, Tadeusz; Elder, David E.; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M.; Goldstein, Alisa M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Hopper, John L.; Ingvar, Christian; Janssen, Marjolein; Jenkins, Mark A.; Kanetsky, Peter A.; Kiemeney, Lambertus A.; Lang, Julie; Lathrop, G. Mark; Leachman, Sancy; Lee, Jeffrey E.; Lubiński, Jan; MacKie, Rona M.; Mann, Graham J.; Martin, Nicholas G.; Mayordomo, Jose I.; Molven, Anders; Mulder, Suzanne; Nagore, Eduardo; Novaković, Srdjan; Okamoto, Ichiro; Olafsson, Jon H.; Olsson, Håkan; Pehamberger, Hubert; Peris, Ketty; Grasa, Maria Pilar; Planelles, Dolores; Puig, Susana; Puig-Butille, Joan Anton; Randerson-Moor, Juliette; Requena, Celia; Rivoltini, Licia; Rodolfo, Monica; Santinami, Mario; Sigurgeirsson, Bardur; Snowden, Helen; Song, Fengju; Sulem, Patrick; Thorisdottir, Kristin; Tuominen, Rainer; Van Belle, Patricia; Van Der Stoep, Nienke; Van Rossum, Michelle M.; Wei, Qingyi; Wendt, Judith; Zelenika, Diana; Zhang, Mingfeng; Landi, Maria Teresa; Thorleifsson, Gudmar; Bishop, D. Timothy; Amos, Christopher I.; Hayward, Nicholas K.; Stefansson, Kari; Bishop, Julia A Newton; Barrett, Jennifer H.

In: Nature Genetics, Vol. 45, No. 4, 04.2013, p. 428-432.

Research output: Contribution to journalArticle

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
Iles MM, Law MH, Stacey SN, Han J, Fang S, Pfeiffer R et al. A variant in FTO shows association with melanoma risk not due to BMI. Nature Genetics. 2013 Apr;45(4):428-432. https://doi.org/10.1038/ng.2571
Iles, Mark M. ; Law, Matthew H. ; Stacey, Simon N. ; Han, Jiali ; Fang, Shenying ; Pfeiffer, Ruth ; Harland, Mark ; MacGregor, Stuart ; Taylor, John C. ; Aben, Katja K. ; Akslen, Lars A. ; Avril, Marie Françoise ; Azizi, Esther ; Bakker, Bert ; Benediktsdottir, Kristrun R. ; Bergman, Wilma ; Scarrà, Giovanna Bianchi ; Brown, Kevin M. ; Calista, Donato ; Chaudru, Valérie ; Fargnoli, Maria Concetta ; Cust, Anne E. ; Demenais, Florence ; De Waal, Anne C. ; Dȩbniak, Tadeusz ; Elder, David E. ; Friedman, Eitan ; Galan, Pilar ; Ghiorzo, Paola ; Gillanders, Elizabeth M. ; Goldstein, Alisa M. ; Gruis, Nelleke A. ; Hansson, Johan ; Helsing, Per ; Hočevar, Marko ; Höiom, Veronica ; Hopper, John L. ; Ingvar, Christian ; Janssen, Marjolein ; Jenkins, Mark A. ; Kanetsky, Peter A. ; Kiemeney, Lambertus A. ; Lang, Julie ; Lathrop, G. Mark ; Leachman, Sancy ; Lee, Jeffrey E. ; Lubiński, Jan ; MacKie, Rona M. ; Mann, Graham J. ; Martin, Nicholas G. ; Mayordomo, Jose I. ; Molven, Anders ; Mulder, Suzanne ; Nagore, Eduardo ; Novaković, Srdjan ; Okamoto, Ichiro ; Olafsson, Jon H. ; Olsson, Håkan ; Pehamberger, Hubert ; Peris, Ketty ; Grasa, Maria Pilar ; Planelles, Dolores ; Puig, Susana ; Puig-Butille, Joan Anton ; Randerson-Moor, Juliette ; Requena, Celia ; Rivoltini, Licia ; Rodolfo, Monica ; Santinami, Mario ; Sigurgeirsson, Bardur ; Snowden, Helen ; Song, Fengju ; Sulem, Patrick ; Thorisdottir, Kristin ; Tuominen, Rainer ; Van Belle, Patricia ; Van Der Stoep, Nienke ; Van Rossum, Michelle M. ; Wei, Qingyi ; Wendt, Judith ; Zelenika, Diana ; Zhang, Mingfeng ; Landi, Maria Teresa ; Thorleifsson, Gudmar ; Bishop, D. Timothy ; Amos, Christopher I. ; Hayward, Nicholas K. ; Stefansson, Kari ; Bishop, Julia A Newton ; Barrett, Jennifer H. / A variant in FTO shows association with melanoma risk not due to BMI. In: Nature Genetics. 2013 ; Vol. 45, No. 4. pp. 428-432.
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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.",
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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.

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