Letter abstract

Nature Genetics 40, 616 - 622 (2008)
Published online: 2 April 2008 | doi:10.1038/ng.109

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

Christopher I Amos1, Xifeng Wu1, Peter Broderick2, Ivan P Gorlov1, Jian Gu1, Timothy Eisen3, Qiong Dong1, Qing Zhang1, Xiangjun Gu1, Jayaram Vijayakrishnan2, Kate Sullivan2, Athena Matakidou2, Yufei Wang2, Gordon Mills4, Kimberly Doheny5, Ya-Yu Tsai5, Wei Vivien Chen1, Sanjay Shete1, Margaret R Spitz1,6 & Richard S Houlston2,6


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 times 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.

  1. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  2. Section of Cancer Genetics, Institute of Cancer Research, SM2 5NG, UK.
  3. Department of Oncology, University of Cambridge, Cambridge CB2 2RE, UK.
  4. Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  5. Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 333 Cassell Drive, Suite 2000, Baltimore, Maryland 21224, USA.
  6. These authors contributed equally to this work.

Correspondence to: Christopher I Amos1 e-mail: camos@mdanderson.org