Meta-analysis and imputation refines the association of 15q25 with smoking quantity

Jason Z. Liu, Federica Tozzi, Dawn M. Waterworth, Sreekumar G. Pillai, Pierandrea Muglia, Lefkos Middleton, Wade Berrettini, Christopher W. Knouff, Xin Yuan, Gérard Waeber, Peter Vollenweider, Martin Preisig, Nicholas J. Wareham, Jing Hua Zhao, Ruth J. F. Loos, Inês Barroso, Kay-Tee Khaw, Scott Grundy, Philip Barter, Robert MahleyAntero Kesaniemi, Ruth McPherson, John B. Vincent, John Strauss, James L. Kennedy, Anne Farmer, Peter McGuffin, Richard Day, Keith Matthews, Per Bakke, Amund Gulsvik, Susanne Lucae, Marcus Ising, Tanja Brueckl, Sonja Horstmann, H-Erich Wichmann, Rajesh Rawal, Norbert Dahmen, Claudia Lamina, Ozren Polasek, Lina Zgaga, Jennifer Huffman, Susan E. Campbell, Jaspal Kooner, John C. Chambers, Mary Susan Burnett, Joseph M. Devaney, Augusto D. Pichard, Kenneth M. Kent, David M. St Clair, Wellcome Trust Case Control Consortium

Research output: Contribution to journalArticlepeer-review

519 Citations (Scopus)


Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.
Original languageEnglish
Pages (from-to)436-440
Number of pages5
JournalNature Genetics
Issue number5
Early online date25 Apr 2010
Publication statusPublished - May 2010


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