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

Authors:
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 Mahley, Antero 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 Campbell, Jaspal Kooner, John C Chambers, Mary Susan Burnett, Joseph M Devaney, Augusto D Pichard, Kenneth M Kent, Lowell Satler, Joseph M Lindsay, Ron Waksman, Stephen Epstein, James F Wilson, Sarah H Wild, Harry Campbell, Veronique Vitart, Muredach P Reilly, Mingyao Li, Liming Qu, Robert Wilensky, William Matthai, Hakon H Hakonarson, Daniel J Rader, Andre Franke, Michael Wittig, Arne Schäfer, Manuela Uda, Antonio Terracciano, Xiangjun Xiao, Fabio Busonero, Paul Scheet, David Schlessinger, David St Clair, Dan Rujescu, Gonçalo R Abecasis, Hans Jörgen Grabe, Alexander Teumer, Henry Völzke, Astrid Petersmann, Ulrich John, Igor Rudan, Caroline Hayward, Alan F Wright, Ivana Kolcic, Benjamin J Wright, John R Thompson, Anthony J Balmforth, Alistair S Hall, Nilesh J Samani, Carl A Anderson, Tariq Ahmad, Christopher G Mathew, Miles Parkes, Jack Satsangi, Mark Caulfield, Patricia B Munroe, Martin Farrall, Anna Dominiczak, Jane Worthington, Wendy Thomson, Steve Eyre, Anne Barton, - -, Vincent Mooser, Clyde Francks, Jonathan Marchini
Year of publication:
2010
Volume:
42
Issue:
5
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
Abstract:
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.