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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Article numberddr154
Pages (from-to)2673-2679
Number of pages7
JournalHuman Molecular Genetics
Volume20
Issue number13
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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Nevi and Melanomas
Genome-Wide Association Study
Melanoma
Skin
Nevus
Alleles
Genotype
Odds Ratio
Confidence Intervals
HapMap Project
Pigmented Nevus
Genes
Single Nucleotide Polymorphism
Cell Line
nidogen

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk. / Nan, Hongmei; Xu, Mousheng; Zhang, Jiangwen; Zhang, Mingfeng; Kraft, Peter; Qureshi, Abrar A.; Chen, Constance; Guo, Qun; Hu, Frank B.; Rimm, Eric B.; Curhan, Gary; Song, Yiqing; Amos, Christopher I.; Wang, Li E.; Lee, Jeffrey E.; Wei, Qingyi; Hunter, David J.; Han, Jiali.

In: Human Molecular Genetics, Vol. 20, No. 13, ddr154, 01.07.2011, p. 2673-2679.

Research output: Contribution to journalArticle

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
Nan, Hongmei ; Xu, Mousheng ; Zhang, Jiangwen ; Zhang, Mingfeng ; Kraft, Peter ; Qureshi, Abrar A. ; Chen, Constance ; Guo, Qun ; Hu, Frank B. ; Rimm, Eric B. ; Curhan, Gary ; Song, Yiqing ; Amos, Christopher I. ; Wang, Li E. ; Lee, Jeffrey E. ; Wei, Qingyi ; Hunter, David J. ; Han, Jiali. / Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 13. pp. 2673-2679.
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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.",
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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.

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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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