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 & 52 others Anne Cust, John Hopper, Kevin M. Brown, Elizabeth A. Grimm, Yaji Xu, Younghun Han, Kaiyan Jing, Caitlin Mchugh, Cathy C. Laurie, Kimberly Doheny, Elizabeth Pugh, Michael F. Seldin, Jiali Han, Qingyi Wei, John L. Hopper, Joanne F. Aitken, Bruce K. Armstrong, Graham G. Giles, Richard F. Kefford, Anne E. Cust, 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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)5012-5023
Number of pages12
JournalHuman molecular genetics
Volume20
Issue number24
DOIs
StatePublished - Dec 1 2011

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Genome-Wide Association Study
Eye Color
Single Nucleotide Polymorphism
Melanoma
Skin Pigmentation
Skin
Chromosomes
Genome
Internal-External Control
Genetic Markers
Computer Simulation
Population
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Amos, C. I., Wang, L. E., Lee, J. E., Gershenwald, J. E., Chen, W. V., Fang, S., ... 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

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

In: Human molecular genetics, Vol. 20, No. 24, 01.12.2011, p. 5012-5023.

Research output: Contribution to journalArticle

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, K, Pugh, E, Seldin, MF, Han, J, Wei, Q, Hopper, JL, Aitken, JF, Armstrong, BK, Giles, GG, Kefford, RF, Cust, AE, 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
Amos CI, Wang LE, Lee JE, Gershenwald JE, Chen WV, Fang S et al. Genome-wide association study identifies novel loci predisposing to cutaneous melanoma. Human molecular genetics. 2011 Dec 1;20(24):5012-5023. https://doi.org/10.1093/hmg/ddr415
Amos, Christopher I. ; Wang, Li E. ; Lee, Jeffrey E. ; Gershenwald, Jeffrey E. ; Chen, Wei V. ; Fang, Shenying ; Kosoy, Roman ; Zhang, Mingfeng ; Qureshi, Abrar A. ; Vattathil, Selina ; Schacherer, Christopher W. ; Gardner, Julie M. ; Wang, Yuling ; Tim bishop, D. ; Barrett, Jennifer H. ; Macgregor, Stuart ; Hayward, Nicholas K. ; Martin, Nicholas G. ; Duffy, David L. ; Mann, Graham J. ; Cust, Anne ; Hopper, John ; Brown, Kevin M. ; Grimm, Elizabeth A. ; Xu, Yaji ; Han, Younghun ; Jing, Kaiyan ; Mchugh, Caitlin ; Laurie, Cathy C. ; Doheny, Kimberly ; Pugh, Elizabeth ; Seldin, Michael F. ; Han, Jiali ; Wei, Qingyi ; Hopper, John L. ; Aitken, Joanne F. ; Armstrong, Bruce K. ; Giles, Graham G. ; Kefford, Richard F. ; Cust, Anne E. ; Jenkins, Mark A. ; Schmid, Helen ; Aguilera, Paula ; Badenas, Celia ; Carrera, Cristina ; Cuellar, Francisco ; Gabriel, Daniel ; Martinez, Estefania ; Gonzalez, Melinda ; Iglesias, Pablo ; Malvehy, Josep ; Marti-Laborda, Rosa ; Mila, Montse ; Ogbah, Zighe ; Puig Butille, Joan Anton ; Puig, Susana ; Alós, Llúcia ; Arance, Ana ; Arguís, Pedro ; Campo, Antonio ; Castel, Teresa ; Conill, Carlos ; Palou, Jose ; Rull, Ramon ; Sánchez, Marcelo ; Vidal-Sicart, Sergi ; Vilalta, Antonio ; Vilella, Ramon ; Montgomery, Grant W. ; Duffy, David L. ; Whiteman, David C. ; Hayward, Nicholas K. / Genome-wide association study identifies novel loci predisposing to cutaneous melanoma. In: Human molecular genetics. 2011 ; Vol. 20, No. 24. pp. 5012-5023.
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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, Kimberly

AU - Pugh, Elizabeth

AU - Seldin, Michael F.

AU - Han, Jiali

AU - Wei, Qingyi

AU - Hopper, John L.

AU - Aitken, Joanne F.

AU - Armstrong, Bruce K.

AU - Giles, Graham G.

AU - Kefford, Richard F.

AU - Cust, Anne E.

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.

PY - 2011/12/1

Y1 - 2011/12/1

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