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

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73 Citazioni (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.

Lingua originale	Inglese
pagine (da-a)	428-428-32, 432e1
Rivista	Nature Genetics
Volume	45
DOI	https://doi.org/10.1038/ng.2571
Stato di pubblicazione	Pubblicato - 2013

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Keywords

Body Mass Index
Case-Control Studies
Cooperative Behavior
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Melanoma
Meta-Analysis as Topic
Obesity
Polymorphism, Single Nucleotide
Proteins
Risk Factors

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10.1038/ng.2571

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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, 428-428-32, 432e1. https://doi.org/10.1038/ng.2571

@article{5d4d41190c4c49928a4a341867a8d599,

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.",

keywords = "Body Mass Index, Case-Control Studies, Cooperative Behavior, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Melanoma, Meta-Analysis as Topic, Obesity, Polymorphism, Single Nucleotide, Proteins, Risk Factors, Body Mass Index, Case-Control Studies, Cooperative Behavior, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Melanoma, Meta-Analysis as Topic, Obesity, Polymorphism, Single Nucleotide, Proteins, Risk Factors",

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 Marie-Fran{\c c}oise Avril 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.\}",

year = "2013",

doi = "10.1038/ng.2571",

language = "English",

volume = "45",

pages = "428--428--32, 432e1",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

}

Iles, MM, Law, MH, Stacey, SN, Han, J, Fang, S, Pfeiffer, R, Harland, M, Macgregor, S, Taylor, JC, Aben, KK, Akslen, LA, Avril, M-F, 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, pagg. 428-428-32, 432e1. 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.

PY - 2013

Y1 - 2013

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.

KW - Body Mass Index

KW - Case-Control Studies

KW - Cooperative Behavior

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Melanoma

KW - Meta-Analysis as Topic

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Risk Factors

KW - Body Mass Index

KW - Case-Control Studies

KW - Cooperative Behavior

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Melanoma

KW - Meta-Analysis as Topic

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Risk Factors

UR - http://hdl.handle.net/10807/56388

U2 - 10.1038/ng.2571

DO - 10.1038/ng.2571

M3 - Article

SN - 1061-4036

VL - 45

SP - 428-428-32, 432e1

JO - Nature Genetics

JF - Nature Genetics

ER -

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

Abstract

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Keywords

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