Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans

Mingfeng Zhang, Fengju Song, Liming Liang, Hongmei Nan, Jiangwen Zhang, Hongliang Liu, Li E. Wang, Qingyi Wei, Jeffrey E. Lee, Christopher I. Amos, Peter Kraft, Abrar A. Qureshi, Jiali Han

Research output: Contribution to journalArticle

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Abstract

Aiming to identify novel genetic loci for pigmentation and skin cancer, we conducted a series of genome-wide association studies on hair color, eye color, number of sunburns, tanning ability and number of non-melanoma skin cancers (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European Americans in the replication stage (for eye color, 3871 males in the discovery stage and 2496 males in the replication stage). We targeted novel chromosome regions besides the known ones for replication. As a result, we identified a new region downstream of the EDNRB gene on 13q22 associated with hair color and the strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P = 2.4 × 10-14; P = 5.4 × 10-9 in the discovery set and P = 1.2 × 10-6 in the replication set). Using blue, intermediate (including green) and brown eye colors as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3 associated with brown eye (P = 7.0 × 10-8; P = 5.3 × 10-5 in the discovery set and P = 0.02 in the replication set). Additionally, we identified a significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2 gene region on brown eye color (P-value for interaction = 3.8 × 10-3). As for the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on chromosome 14: rs12203592 in IRF4 (P = 7.2 × 10-14; P = 1.8 × 10-8 in the discovery set and P = 6.7 × 10-7 in the replication set), rs12202284 between IRF4 and EXOC2 (P = 5.0 × 10-8; P = 6.6 × 10-7 in the discovery set and P = 3.0 × 10-3 in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10-8; P = 5.3 × 10-7 in the discovery set and P = 0.01 in the replication set).

Original languageEnglish (US)
Article numberddt142
Pages (from-to)2948-2959
Number of pages12
JournalHuman molecular genetics
Volume22
Issue number14
DOIs
StatePublished - Jul 1 2013

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Eye Color
Genome-Wide Association Study
Pigmentation
Skin Neoplasms
Single Nucleotide Polymorphism
Hair Color
Tanning
Sunburn
Chromosomes, Human, Pair 14
Genetic Loci
Genes
Chromosomes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans. / Zhang, Mingfeng; Song, Fengju; Liang, Liming; Nan, Hongmei; Zhang, Jiangwen; Liu, Hongliang; Wang, Li E.; Wei, Qingyi; Lee, Jeffrey E.; Amos, Christopher I.; Kraft, Peter; Qureshi, Abrar A.; Han, Jiali.

In: Human molecular genetics, Vol. 22, No. 14, ddt142, 01.07.2013, p. 2948-2959.

Research output: Contribution to journalArticle

Zhang, M, Song, F, Liang, L, Nan, H, Zhang, J, Liu, H, Wang, LE, Wei, Q, Lee, JE, Amos, CI, Kraft, P, Qureshi, AA & Han, J 2013, 'Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans', Human molecular genetics, vol. 22, no. 14, ddt142, pp. 2948-2959. https://doi.org/10.1093/hmg/ddt142
Zhang, Mingfeng ; Song, Fengju ; Liang, Liming ; Nan, Hongmei ; Zhang, Jiangwen ; Liu, Hongliang ; Wang, Li E. ; Wei, Qingyi ; Lee, Jeffrey E. ; Amos, Christopher I. ; Kraft, Peter ; Qureshi, Abrar A. ; Han, Jiali. / Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans. In: Human molecular genetics. 2013 ; Vol. 22, No. 14. pp. 2948-2959.
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abstract = "Aiming to identify novel genetic loci for pigmentation and skin cancer, we conducted a series of genome-wide association studies on hair color, eye color, number of sunburns, tanning ability and number of non-melanoma skin cancers (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European Americans in the replication stage (for eye color, 3871 males in the discovery stage and 2496 males in the replication stage). We targeted novel chromosome regions besides the known ones for replication. As a result, we identified a new region downstream of the EDNRB gene on 13q22 associated with hair color and the strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P = 2.4 × 10-14; P = 5.4 × 10-9 in the discovery set and P = 1.2 × 10-6 in the replication set). Using blue, intermediate (including green) and brown eye colors as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3 associated with brown eye (P = 7.0 × 10-8; P = 5.3 × 10-5 in the discovery set and P = 0.02 in the replication set). Additionally, we identified a significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2 gene region on brown eye color (P-value for interaction = 3.8 × 10-3). As for the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on chromosome 14: rs12203592 in IRF4 (P = 7.2 × 10-14; P = 1.8 × 10-8 in the discovery set and P = 6.7 × 10-7 in the replication set), rs12202284 between IRF4 and EXOC2 (P = 5.0 × 10-8; P = 6.6 × 10-7 in the discovery set and P = 3.0 × 10-3 in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10-8; P = 5.3 × 10-7 in the discovery set and P = 0.01 in the replication set).",
author = "Mingfeng Zhang and Fengju Song and Liming Liang and Hongmei Nan and Jiangwen Zhang and Hongliang Liu and Wang, {Li E.} and Qingyi Wei and Lee, {Jeffrey E.} and Amos, {Christopher I.} and Peter Kraft and Qureshi, {Abrar A.} and Jiali Han",
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AU - Wei, Qingyi

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N2 - Aiming to identify novel genetic loci for pigmentation and skin cancer, we conducted a series of genome-wide association studies on hair color, eye color, number of sunburns, tanning ability and number of non-melanoma skin cancers (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European Americans in the replication stage (for eye color, 3871 males in the discovery stage and 2496 males in the replication stage). We targeted novel chromosome regions besides the known ones for replication. As a result, we identified a new region downstream of the EDNRB gene on 13q22 associated with hair color and the strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P = 2.4 × 10-14; P = 5.4 × 10-9 in the discovery set and P = 1.2 × 10-6 in the replication set). Using blue, intermediate (including green) and brown eye colors as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3 associated with brown eye (P = 7.0 × 10-8; P = 5.3 × 10-5 in the discovery set and P = 0.02 in the replication set). Additionally, we identified a significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2 gene region on brown eye color (P-value for interaction = 3.8 × 10-3). As for the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on chromosome 14: rs12203592 in IRF4 (P = 7.2 × 10-14; P = 1.8 × 10-8 in the discovery set and P = 6.7 × 10-7 in the replication set), rs12202284 between IRF4 and EXOC2 (P = 5.0 × 10-8; P = 6.6 × 10-7 in the discovery set and P = 3.0 × 10-3 in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10-8; P = 5.3 × 10-7 in the discovery set and P = 0.01 in the replication set).

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