Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1

Christopher I. Amos, Xifeng Wu, Peter Broderick, Ivan P. Gorlov, Jian Gu, Timothy Eisen, Qiong Dong, Qing Zhang, Xiangjun Gu, Jayaram Vijayakrishnan, Kate Sullivan, Athena Matakidou, Yufei Wang, Gordon Mills, Kimberly Doheny, Ya Yu Tsai, Wei Vivien Chen, Sanjay Shete, Margaret R. Spitz, Richard S. Houlston

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Abstract

To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 × 10-17) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.

Original languageEnglish (US)
Pages (from-to)616-622
Number of pages7
JournalNature Genetics
Volume40
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Genome-Wide Association Study
Single Nucleotide Polymorphism
Lung Neoplasms
Nicotinic Receptors
Smoking
Linkage Disequilibrium
Haplotypes
Genes
Odds Ratio

ASJC Scopus subject areas

  • Genetics

Cite this

Amos, C. I., Wu, X., Broderick, P., Gorlov, I. P., Gu, J., Eisen, T., ... Houlston, R. S. (2008). Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nature Genetics, 40(5), 616-622. https://doi.org/10.1038/ng.109

Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. / Amos, Christopher I.; Wu, Xifeng; Broderick, Peter; Gorlov, Ivan P.; Gu, Jian; Eisen, Timothy; Dong, Qiong; Zhang, Qing; Gu, Xiangjun; Vijayakrishnan, Jayaram; Sullivan, Kate; Matakidou, Athena; Wang, Yufei; Mills, Gordon; Doheny, Kimberly; Tsai, Ya Yu; Chen, Wei Vivien; Shete, Sanjay; Spitz, Margaret R.; Houlston, Richard S.

In: Nature Genetics, Vol. 40, No. 5, 01.05.2008, p. 616-622.

Research output: Contribution to journalArticle

Amos, CI, Wu, X, Broderick, P, Gorlov, IP, Gu, J, Eisen, T, Dong, Q, Zhang, Q, Gu, X, Vijayakrishnan, J, Sullivan, K, Matakidou, A, Wang, Y, Mills, G, Doheny, K, Tsai, YY, Chen, WV, Shete, S, Spitz, MR & Houlston, RS 2008, 'Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1', Nature Genetics, vol. 40, no. 5, pp. 616-622. https://doi.org/10.1038/ng.109
Amos, Christopher I. ; Wu, Xifeng ; Broderick, Peter ; Gorlov, Ivan P. ; Gu, Jian ; Eisen, Timothy ; Dong, Qiong ; Zhang, Qing ; Gu, Xiangjun ; Vijayakrishnan, Jayaram ; Sullivan, Kate ; Matakidou, Athena ; Wang, Yufei ; Mills, Gordon ; Doheny, Kimberly ; Tsai, Ya Yu ; Chen, Wei Vivien ; Shete, Sanjay ; Spitz, Margaret R. ; Houlston, Richard S. / Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. In: Nature Genetics. 2008 ; Vol. 40, No. 5. pp. 616-622.
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