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

    Research output: Contribution to journalArticle

    942 Scopus citations

    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 2008

    ASJC Scopus subject areas

    • Genetics

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  • Cite this

    Amos, C. I., Wu, X., Broderick, P., Gorlov, I. P., Gu, J., Eisen, T., Dong, Q., Zhang, Q., Gu, X., Vijayakrishnan, J., Sullivan, K., Matakidou, A., Wang, Y., Mills, G., Doheny, K., Tsai, Y. Y., Chen, W. V., Shete, S., Spitz, M. R., & 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