Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk

Hongmei Nan; Mousheng Xu; Jiangwen Zhang; Mingfeng Zhang; Peter Kraft; Abrar A. Qureshi; Constance Chen; Qun Guo; Frank B. Hu; Eric B. Rimm; Gary Curhan; Yiqing Song; Christopher I. Amos; Li E. Wang; Jeffrey E. Lee; Qingyi Wei; David J. Hunter; Jiali Han

doi:10.1093/hmg/ddr154

Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk

Hongmei Nan, Mousheng Xu, Jiangwen Zhang, Mingfeng Zhang, Peter Kraft, Abrar A. Qureshi, Constance Chen, Qun Guo, Frank B. Hu, Eric B. Rimm, Gary Curhan, Yiqing Song, Christopher I. Amos, Li E. Wang, Jeffrey E. Lee, Qingyi Wei, David J. Hunter, Jiali Han

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Abstract

We conducted a genome-wide association study on the number of melanocytic nevi reported by 9136 individuals of European ancestry, with follow-up replication in 3581 individuals. We identified the nidogen 1 (NID1) gene on 1q42 associated with nevus count (two linked single nucleotide polymorphisms with r² > 0.9: rs3768080 A allele associated with reduced count, P = 6.5 × 10^-8; and rs10754833 T allele associated with reduced count, P = 1.5 × 10^-7). We further determined that the rs10754833 [T] was associated with a decreased melanoma risk in 2368 melanoma cases and 7432 controls [for CT genotype: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, P = 0.04; for TT genotype: OR = 0.84, 95% CI = 0.71-0.98, P = 0.03]. Expression level of the NID1 locus was 2-fold higher for the rs10754833 T allele carriers than that with the CC genotype (P = 0.017) in the 87 HapMap CEU cell lines. The NID1 gene is a biologically plausible locus for nevogenesis and melanoma development, with decreased expression levels of NID1 in benign nevi (P = 3.5 × 10^-6) and in primary melanoma (P = 4.6 × 10^-4) compared with the normal skin.

Original language	English (US)
Article number	ddr154
Pages (from-to)	2673-2679
Number of pages	7
Journal	Human molecular genetics
Volume	20
Issue number	13
DOIs	https://doi.org/10.1093/hmg/ddr154
State	Published - Jul 2011

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Nan, H., Xu, M., Zhang, J., Zhang, M., Kraft, P., Qureshi, A. A., Chen, C., Guo, Q., Hu, F. B., Rimm, E. B., Curhan, G., Song, Y., Amos, C. I., Wang, L. E., Lee, J. E., Wei, Q., Hunter, D. J., & Han, J. (2011). Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk. Human molecular genetics, 20(13), 2673-2679. Article ddr154. https://doi.org/10.1093/hmg/ddr154

Nan, H, Xu, M, Zhang, J, Zhang, M, Kraft, P, Qureshi, AA, Chen, C, Guo, Q, Hu, FB, Rimm, EB, Curhan, G, Song, Y, Amos, CI, Wang, LE, Lee, JE, Wei, Q, Hunter, DJ & Han, J 2011, 'Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk', Human molecular genetics, vol. 20, no. 13, ddr154, pp. 2673-2679. https://doi.org/10.1093/hmg/ddr154

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title = "Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk",

abstract = "We conducted a genome-wide association study on the number of melanocytic nevi reported by 9136 individuals of European ancestry, with follow-up replication in 3581 individuals. We identified the nidogen 1 (NID1) gene on 1q42 associated with nevus count (two linked single nucleotide polymorphisms with r2 > 0.9: rs3768080 A allele associated with reduced count, P = 6.5 × 10-8; and rs10754833 T allele associated with reduced count, P = 1.5 × 10-7). We further determined that the rs10754833 [T] was associated with a decreased melanoma risk in 2368 melanoma cases and 7432 controls [for CT genotype: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, P = 0.04; for TT genotype: OR = 0.84, 95% CI = 0.71-0.98, P = 0.03]. Expression level of the NID1 locus was 2-fold higher for the rs10754833 T allele carriers than that with the CC genotype (P = 0.017) in the 87 HapMap CEU cell lines. The NID1 gene is a biologically plausible locus for nevogenesis and melanoma development, with decreased expression levels of NID1 in benign nevi (P = 3.5 × 10-6) and in primary melanoma (P = 4.6 × 10-4) compared with the normal skin.",

author = "Hongmei Nan and Mousheng Xu and Jiangwen Zhang and Mingfeng Zhang and Peter Kraft and Qureshi, {Abrar A.} and Constance Chen and Qun Guo and Hu, {Frank B.} and Rimm, {Eric B.} and Gary Curhan and Yiqing Song and Amos, {Christopher I.} and Wang, {Li E.} and Lee, {Jeffrey E.} and Qingyi Wei and Hunter, {David J.} and Jiali Han",

year = "2011",

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doi = "10.1093/hmg/ddr154",

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T1 - Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk

AU - Nan, Hongmei

AU - Xu, Mousheng

AU - Zhang, Jiangwen

AU - Zhang, Mingfeng

AU - Kraft, Peter

AU - Qureshi, Abrar A.

AU - Chen, Constance

AU - Guo, Qun

AU - Hu, Frank B.

AU - Rimm, Eric B.

AU - Curhan, Gary

AU - Song, Yiqing

AU - Amos, Christopher I.

AU - Wang, Li E.

AU - Lee, Jeffrey E.

AU - Wei, Qingyi

AU - Hunter, David J.

AU - Han, Jiali

PY - 2011/7

Y1 - 2011/7

N2 - We conducted a genome-wide association study on the number of melanocytic nevi reported by 9136 individuals of European ancestry, with follow-up replication in 3581 individuals. We identified the nidogen 1 (NID1) gene on 1q42 associated with nevus count (two linked single nucleotide polymorphisms with r2 > 0.9: rs3768080 A allele associated with reduced count, P = 6.5 × 10-8; and rs10754833 T allele associated with reduced count, P = 1.5 × 10-7). We further determined that the rs10754833 [T] was associated with a decreased melanoma risk in 2368 melanoma cases and 7432 controls [for CT genotype: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, P = 0.04; for TT genotype: OR = 0.84, 95% CI = 0.71-0.98, P = 0.03]. Expression level of the NID1 locus was 2-fold higher for the rs10754833 T allele carriers than that with the CC genotype (P = 0.017) in the 87 HapMap CEU cell lines. The NID1 gene is a biologically plausible locus for nevogenesis and melanoma development, with decreased expression levels of NID1 in benign nevi (P = 3.5 × 10-6) and in primary melanoma (P = 4.6 × 10-4) compared with the normal skin.

AB - We conducted a genome-wide association study on the number of melanocytic nevi reported by 9136 individuals of European ancestry, with follow-up replication in 3581 individuals. We identified the nidogen 1 (NID1) gene on 1q42 associated with nevus count (two linked single nucleotide polymorphisms with r2 > 0.9: rs3768080 A allele associated with reduced count, P = 6.5 × 10-8; and rs10754833 T allele associated with reduced count, P = 1.5 × 10-7). We further determined that the rs10754833 [T] was associated with a decreased melanoma risk in 2368 melanoma cases and 7432 controls [for CT genotype: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, P = 0.04; for TT genotype: OR = 0.84, 95% CI = 0.71-0.98, P = 0.03]. Expression level of the NID1 locus was 2-fold higher for the rs10754833 T allele carriers than that with the CC genotype (P = 0.017) in the 87 HapMap CEU cell lines. The NID1 gene is a biologically plausible locus for nevogenesis and melanoma development, with decreased expression levels of NID1 in benign nevi (P = 3.5 × 10-6) and in primary melanoma (P = 4.6 × 10-4) compared with the normal skin.

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Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk

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