Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21926416
TITLE
Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.
ABSTRACT
We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
DATE PUBLISHED
2011 Dec 15
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/09/17
aheadofprint 2011/09/22
entrez 2011/09/20 06:00
pubmed 2011/09/20 06:00
medline 2012/03/09 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Amos CI Amos Christopher I CI Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. camos@mdanderson.org
Wang LE Wang Li-E LE
Lee JE Lee Jeffrey E JE
Gershenwald JE Gershenwald Jeffrey E JE
Chen WV Chen Wei V WV
Fang S Fang Shenying S
Kosoy R Kosoy Roman R
Zhang M Zhang Mingfeng M
Qureshi AA Qureshi Abrar A AA
Vattathil S Vattathil Selina S
Schacherer CW Schacherer Christopher W CW
Gardner JM Gardner Julie M JM
Wang Y Wang Yuling Y
Bishop DT Bishop D Tim DT
Barrett JH Barrett Jennifer H JH
GenoMEL Investigators
MacGregor S MacGregor Stuart S
Hayward NK Hayward Nicholas K NK
Martin NG Martin Nicholas G NG
Duffy DL Duffy David L DL
Q-Mega Investigators
Mann GJ Mann Graham J GJ
Cust A Cust Anne A
Hopper J Hopper John J
AMFS Investigators
Brown KM Brown Kevin M KM
Grimm EA Grimm Elizabeth A EA
Xu Y Xu Yaji Y
Han Y Han Younghun Y
Jing K Jing Kaiyan K
McHugh C McHugh Caitlin C
Laurie CC Laurie Cathy C CC
Doheny KF Doheny Kim F KF
Pugh EW Pugh Elizabeth W EW
Seldin MF Seldin Michael F MF
Han J Han Jiali J
Wei Q Wei Qingyi Q
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Mann Graham J GJ
Hopper John L JL
Aitken Joanne F JF
Armstrong Bruce K BK
Giles Graham G GG
Kefford Richard F RF
Cust Anne E AE
Jenkins Mark A MA
Schmid Helen H
Aguilera Paula P
Badenas Celia C
Carrera Cristina C
Cuellar Francisco F
Gabriel Daniel D
Martinez Estefania E
Gonzalez Melinda M
Iglesias Pablo P
Malvehy Josep J
Marti-Laborda Rosa R
Mila Montse M
Ogbah Zighe Z
Butille Joan-Anton Puig JA
Puig Susana S
Alós Llúcia L
Arance Ana A
Arguís Pedro P
Campo Antonio A
Castel Teresa T
Conill Carlos C
Palou Jose J
Rull Ramon R
Sánchez Marcelo M
Vidal-Sicart Sergi S
Vilalta Antonio A
Vilella Ramon R
Martin Nicholas G NG
Montgomery Grant W GW
Duffy David L DL
Whiteman David C DC
MacGregor Stuart S
Hayward Nicholas K NK
Whiteman David D
Webb Penny P
Green Adele A
Parsons Peter P
Purdie David D
Hayward Nicholas N
Landi Maria Teresa MT
Calista Donato D
Landi Giorgio G
Minghetti Paola P
Arcangeli Fabio F
Bertazzi Pier Alberto PA
Bianchi-Scarra Giovanna G
Ghiorzo Paola P
Pastorino Lorenza L
Bruno William W
Battistuzzi Linda L
Gargiulo Sara S
Nasti Sabina S
Gliori Sara S
Origone Paola P
Andreotti Virginia V
Queirolo Paola P
Mackie Rona R
Lang Julie J
Bishop Julia A Newton JA
Affleck Paul P
Barrett Jennifer H JH
Bishop D Timothy DT
Harrison Jane J
Iles Mark M MM
Randerson-Moor Juliette J
Harland Mark M
Taylor John C JC
Whittaker Linda L
Kukalizch Kairen K
Leake Susan S
Karpavicius Birute B
Haynes Sue S
Mack Tricia T
Chan May M
Taylor Yvonne Y
Davies John J
King Paul P
Gruis Nelleke A NA
van Nieuwpoort Frans A FA
Out Coby C
van der Drift Clasine C
Bergman Wilma W
Kukutsch Nicole N
Bavinck Jan Nico Bouwes JN
Bakker Bert B
van der Stoep Nienke N
ter Huurne Jeanet J
van der Rhee Han H
Bekkenk Marcel M
Snels Dyon D
van Praag Marinus M
Brochez Lieve L
Gerritsen Rianne R
Crijns Marianne M
Vasen Hans H
Olsson Håkan H
Ingvar Christian C
Jönsson Göran G
Borg Åke
Måsbäck Anna A
Lundgren Lotta L
Baeckenhorn Katja K
Nielsen Kari K
Casslén Anita Schmidt AS
Helsing Per P
Andresen Per Arne PA
Rootwelt Helge H
Akslen Lars A LA
Molven Anders A
Avril Marie-Françoise MF
Bressac-de Paillerets Brigitte B
Chaudru Valérie V
Chateigner Nicolas N
Corda Eve E
Jeannin Patricia P
Lesueur Fabienne F
de Lichy Mahaut M
Maubec Eve E
Mohamdi Hamida H
Demenais Florence F
Andry-Benzaquen Pascale P
Bachollet Bertrand B
Bérard Frédéric F
Berthet Pascaline P
Boitier Françoise F
Bonadona Valérie V
Bonafé Jean-Louis JL
Bonnetblanc Jean-Marie JM
Cambazard Frédéric F
Caron Olivier O
Caux Frédéric F
Chevrant-Breton Jacqueline J
Chompret Agnès A
Dalle Stéphane S
Demange Liliane L
Dereure Olivier O
Doré Martin-Xavier MX
Doutre Marie-Sylvie MS
Dugast Catherine C
Faivre Laurence L
Grange Florent F
Humbert Philippe P
Joly Pascal P
Kerob Delphine D
Lasset Christine C
Leccia Marie Thérèse MT
Lenoir Gilbert G
Leroux Dominique D
Levang Julien J
Lipsker Dan D
Mansard Sandrine S
Martin Ludovic L
Martin-Denavit Tanguy T
Mateus Christine C
Michel Jean-Loïc JL
Morel Patrice P
Olivier-Faivre Laurence L
Perrot Jean-Luc JL
Robert Caroline C
Ronger-Savle Sandra S
Sassolas Bruno B
Souteyrand Pierre P
Stoppa-Lyonnet Dominique D
Thomas Luc L
Vabres Pierre P
Wierzbicka Eva E
Elder David D
Kanetsky Peter P
Knorr Jillian J
Ming Michael M
Mitra Nandita N
Ruffin Althea A
Van Belle Patricia P
Debniak Tadeusz T
Lubiński Jan J
Mirecka Aneta A
Ertmański Sławomir S
Novakovic Srdjan S
Hocevar Marko M
Peric Barbara B
Cerkovnik Petra P
Höiom Veronica V
Hansson Johan J
Mann Graham J GJ
Kefford Richard F RF
Schmid Helen H
Holland Elizabeth A EA
Azizi Esther E
Galore-Haskel Gilli G
Friedman Eitan E
Baron-Epel Orna O
Scope Alon A
Pavlotsky Felix F
Yakobson Emanuel E
Cohen-Manheim Irit I
Laitman Yael Y
Milgrom Roni R
Shimoni Iris I
Kozlovaa Evgeniya E
JOURNAL
VOLUME: 20
ISSUE: 24
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2011
MONTH: Dec
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
10589 Cancer Research UK United Kingdom
2P50CA093459 NCI NIH HHS United States
C588/A10589 Cancer Research UK United Kingdom
C588/A4994 Cancer Research UK United Kingdom
C8216/A6129 Cancer Research UK United Kingdom
HG004446 NHGRI NIH HHS United States
HHSN268200782096C PHS HHS United States
P30CA016672 NCI NIH HHS United States
R01 CA-83115-01A2 NCI NIH HHS United States
R01 CA137365 NCI NIH HHS United States
R01 CA83115 NCI NIH HHS United States
R01CA100264 NCI NIH HHS United States
R01CA133996 NCI NIH HHS United States
Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Case-Control Studies
Chromosomes, Human, Pair 1 genetics
Genetic Loci genetics
Genetic Markers genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Guanine Nucleotide Exchange Factors genetics
Humans genetics
Melanoma genetics
Meta-Analysis as Topic genetics
Pigmentation genetics
Polymorphism, Single Nucleotide genetics
Skin Neoplasms genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
0 Guanine Nucleotide Exchange Factors
0 HERC2 protein, human
OTHER ID's
OTHERID SOURCE
PMC3298855 NLM