Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

Christopher I. Amos; Li E. Wang; Jeffrey E. Lee; Jeffrey E. Gershenwald; Wei V. Chen; Shenying Fang; Roman Kosoy; Mingfeng Zhang; Abrar A. Qureshi; Selina Vattathil; Christopher W. Schacherer; Julie M. Gardner; Yuling Wang; D. Tim bishop; Jennifer H. Barrett; Stuart Macgregor; Nicholas K. Hayward; Nicholas G. Martin; David L. Duffy; Graham J. Mann; Anne Cust; John Hopper; Kevin M. Brown; Elizabeth A. Grimm; Yaji Xu; Younghun Han; Kaiyan Jing; Caitlin Mchugh; Cathy C. Laurie; Kim F. Doheny; Elizabeth W. Pugh; Michael F. Seldin; Jiali Han; Qingyi Wei; Joanne F. Aitken; Bruce K. Armstrong; Graham G. Giles; Richard F. Kefford; Mark A. Jenkins; Helen Schmid; Paula Aguilera; Celia Badenas; Cristina Carrera; Francisco Cuellar; Daniel Gabriel; Estefania Martinez; Melinda Gonzalez; Pablo Iglesias; Josep Malvehy; Rosa Marti-Laborda; Montse Mila; Zighe Ogbah; Joan Anton Puig Butille; Susana Puig; Llúcia Alós; Ana Arance; Pedro Arguís; Antonio Campo; Teresa Castel; Carlos Conill; Jose Palou; Ramon Rull; Marcelo Sánchez; Sergi Vidal-Sicart; Antonio Vilalta; Ramon Vilella; Grant W. Montgomery; David L. Duffy; David C. Whiteman; Nicholas K. Hayward

doi:10.1093/hmg/ddr415

Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

Christopher I. Amos, Li E. Wang, Jeffrey E. Lee, Jeffrey E. Gershenwald, Wei V. Chen, Shenying Fang, Roman Kosoy, Mingfeng Zhang, Abrar A. Qureshi, Selina Vattathil, Christopher W. Schacherer, Julie M. Gardner, Yuling Wang, D. Tim bishop, Jennifer H. Barrett, Stuart Macgregor, Nicholas K. Hayward, Nicholas G. Martin, David L. Duffy, Graham J. MannAnne Cust, John Hopper, Kevin M. Brown, Elizabeth A. Grimm, Yaji Xu, Younghun Han, Kaiyan Jing, Caitlin Mchugh, Cathy C. Laurie, Kim F. Doheny, Elizabeth W. Pugh, Michael F. Seldin, Jiali Han, Qingyi Wei, Joanne F. Aitken, Bruce K. Armstrong, Graham G. Giles, Richard F. Kefford, Mark A. Jenkins, Helen Schmid, Paula Aguilera, Celia Badenas, Cristina Carrera, Francisco Cuellar, Daniel Gabriel, Estefania Martinez, Melinda Gonzalez, Pablo Iglesias, Josep Malvehy, Rosa Marti-Laborda, Montse Mila, Zighe Ogbah, Joan Anton Puig Butille, Susana Puig, Llúcia Alós, Ana Arance, Pedro Arguís, Antonio Campo, Teresa Castel, Carlos Conill, Jose Palou, Ramon Rull, Marcelo Sánchez, Sergi Vidal-Sicart, Antonio Vilalta, Ramon Vilella, Grant W. Montgomery, David L. Duffy, David C. Whiteman, Nicholas K. Hayward

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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.

Original language	English (US)
Pages (from-to)	5012-5023
Number of pages	12
Journal	Human molecular genetics
Volume	20
Issue number	24
DOIs	https://doi.org/10.1093/hmg/ddr415
State	Published - Dec 1 2011

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Amos, C. I., Wang, L. E., Lee, J. E., Gershenwald, J. E., Chen, W. V., Fang, S., Kosoy, R., Zhang, M., Qureshi, A. A., Vattathil, S., Schacherer, C. W., Gardner, J. M., Wang, Y., Tim bishop, D., Barrett, J. H., Macgregor, S., Hayward, N. K., Martin, N. G., Duffy, D. L., ... Hayward, N. K. (2011). Genome-wide association study identifies novel loci predisposing to cutaneous melanoma. Human molecular genetics, 20(24), 5012-5023. https://doi.org/10.1093/hmg/ddr415

Amos, CI, Wang, LE, Lee, JE , Gershenwald, JE , Chen, WV, Fang, S, Kosoy, R, Zhang, M, Qureshi, AA, Vattathil, S, Schacherer, CW, Gardner, JM, Wang, Y, Tim bishop, D, Barrett, JH, Macgregor, S, Hayward, NK, Martin, NG, Duffy, DL, Mann, GJ, Cust, A, Hopper, J, Brown, KM, Grimm, EA, Xu, Y, Han, Y, Jing, K, Mchugh, C, Laurie, CC, Doheny, KF, Pugh, EW, Seldin, MF, Han, J, Wei, Q, Aitken, JF, Armstrong, BK, Giles, GG, Kefford, RF, Jenkins, MA, Schmid, H, Aguilera, P, Badenas, C, Carrera, C, Cuellar, F, Gabriel, D, Martinez, E, Gonzalez, M, Iglesias, P, Malvehy, J, Marti-Laborda, R, Mila, M, Ogbah, Z, Puig Butille, JA, Puig, S, Alós, L, Arance, A, Arguís, P, Campo, A, Castel, T, Conill, C, Palou, J, Rull, R, Sánchez, M, Vidal-Sicart, S, Vilalta, A, Vilella, R, Montgomery, GW, Duffy, DL, Whiteman, DC & Hayward, NK 2011, 'Genome-wide association study identifies novel loci predisposing to cutaneous melanoma', Human molecular genetics, vol. 20, no. 24, pp. 5012-5023. https://doi.org/10.1093/hmg/ddr415

@article{86b66a4aa69644ce8fae338271be0f7f,

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.",

author = "Amos, {Christopher I.} and Wang, {Li E.} and Lee, {Jeffrey E.} and Gershenwald, {Jeffrey E.} and Chen, {Wei V.} and Shenying Fang and Roman Kosoy and Mingfeng Zhang and Qureshi, {Abrar A.} and Selina Vattathil and Schacherer, {Christopher W.} and Gardner, {Julie M.} and Yuling Wang and {Tim bishop}, D. and Barrett, {Jennifer H.} and Stuart Macgregor and Hayward, {Nicholas K.} and Martin, {Nicholas G.} and Duffy, {David L.} and Mann, {Graham J.} and Anne Cust and John Hopper and Brown, {Kevin M.} and Grimm, {Elizabeth A.} and Yaji Xu and Younghun Han and Kaiyan Jing and Caitlin Mchugh and Laurie, {Cathy C.} and Doheny, {Kim F.} and Pugh, {Elizabeth W.} and Seldin, {Michael F.} and Jiali Han and Qingyi Wei and Aitken, {Joanne F.} and Armstrong, {Bruce K.} and Giles, {Graham G.} and Kefford, {Richard F.} and Jenkins, {Mark A.} and Helen Schmid and Paula Aguilera and Celia Badenas and Cristina Carrera and Francisco Cuellar and Daniel Gabriel and Estefania Martinez and Melinda Gonzalez and Pablo Iglesias and Josep Malvehy and Rosa Marti-Laborda and Montse Mila and Zighe Ogbah and {Puig Butille}, {Joan Anton} and Susana Puig and Ll{\'u}cia Al{\'o}s and Ana Arance and Pedro Argu{\'i}s and Antonio Campo and Teresa Castel and Carlos Conill and Jose Palou and Ramon Rull and Marcelo S{\'a}nchez and Sergi Vidal-Sicart and Antonio Vilalta and Ramon Vilella and Montgomery, {Grant W.} and Duffy, {David L.} and Whiteman, {David C.} and Hayward, {Nicholas K.}",

note = "Funding Information: Lund: Swedish Cancer Society, Swedish Research Council, Region Sk{\aa}ne funds, Kamprad Foundation.",

year = "2011",

month = dec,

day = "1",

doi = "10.1093/hmg/ddr415",

language = "English (US)",

volume = "20",

pages = "5012--5023",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "24",

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TY - JOUR

T1 - Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

AU - Amos, Christopher I.

AU - Wang, Li E.

AU - Lee, Jeffrey E.

AU - Gershenwald, Jeffrey E.

AU - Chen, Wei V.

AU - Fang, Shenying

AU - Kosoy, Roman

AU - Zhang, Mingfeng

AU - Qureshi, Abrar A.

AU - Vattathil, Selina

AU - Schacherer, Christopher W.

AU - Gardner, Julie M.

AU - Wang, Yuling

AU - Tim bishop, D.

AU - Barrett, Jennifer H.

AU - Macgregor, Stuart

AU - Hayward, Nicholas K.

AU - Martin, Nicholas G.

AU - Duffy, David L.

AU - Mann, Graham J.

AU - Cust, Anne

AU - Hopper, John

AU - Brown, Kevin M.

AU - Grimm, Elizabeth A.

AU - Xu, Yaji

AU - Han, Younghun

AU - Jing, Kaiyan

AU - Mchugh, Caitlin

AU - Laurie, Cathy C.

AU - Doheny, Kim F.

AU - Pugh, Elizabeth W.

AU - Seldin, Michael F.

AU - Han, Jiali

AU - Wei, Qingyi

AU - Aitken, Joanne F.

AU - Armstrong, Bruce K.

AU - Giles, Graham G.

AU - Kefford, Richard F.

AU - Jenkins, Mark A.

AU - Schmid, Helen

AU - Aguilera, Paula

AU - Badenas, Celia

AU - Carrera, Cristina

AU - Cuellar, Francisco

AU - Gabriel, Daniel

AU - Martinez, Estefania

AU - Gonzalez, Melinda

AU - Iglesias, Pablo

AU - Malvehy, Josep

AU - Marti-Laborda, Rosa

AU - Mila, Montse

AU - Ogbah, Zighe

AU - Puig Butille, Joan Anton

AU - Puig, Susana

AU - Alós, Llúcia

AU - Arance, Ana

AU - Arguís, Pedro

AU - Campo, Antonio

AU - Castel, Teresa

AU - Conill, Carlos

AU - Palou, Jose

AU - Rull, Ramon

AU - Sánchez, Marcelo

AU - Vidal-Sicart, Sergi

AU - Vilalta, Antonio

AU - Vilella, Ramon

AU - Montgomery, Grant W.

AU - Duffy, David L.

AU - Whiteman, David C.

AU - Hayward, Nicholas K.

N1 - Funding Information: Lund: Swedish Cancer Society, Swedish Research Council, Region Skåne funds, Kamprad Foundation.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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.

AB - 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.

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U2 - 10.1093/hmg/ddr415

DO - 10.1093/hmg/ddr415

M3 - Article

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AN - SCOPUS:81855199793

SN - 0964-6906

VL - 20

SP - 5012

EP - 5023

JO - Human molecular genetics

JF - Human molecular genetics

IS - 24

ER -

Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

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