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

Smoking is a leading global cause of disease and mortality1. 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 × 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.

Tariq Ahmad | Inês Barroso | Lowell Satler | Paul Scheet | Alexander Teumer | Lefkos Middleton | Henry Völzke | William Matthai | Vincent Mooser | Igor Rudan | Xiangjun Xiao | Jing Hua Zhao | Christopher G Mathew | Nilesh J Samani | Andre Franke | Keith Matthews | Harry Campbell | David Schlessinger | Nicholas J Wareham | Caroline Hayward | Muredach P Reilly | Norbert Dahmen | Lina Zgaga | Gérard Waeber | Jack Satsangi | Wendy Thomson | Arne Schäfer | Jaspal Kooner | Ruth McPherson | Jonathan Marchini | Peter McGuffin | Martin Farrall | Fabio Busonero | Pierandrea Muglia | Antonio Terracciano | Anne Barton | John Strauss | Claudia Lamina | Michael Wittig | John C Chambers | Miles Parkes | Astrid Petersmann | Hans Jörgen Grabe | Kay-Tee Khaw | Anne Farmer | Ozren Polasek | Jennifer Huffman | Amund Gulsvik | Liming Qu | Gonçalo R Abecasis | Ron Waksman | Veronique Vitart | Ivana Kolcic | Carl A Anderson | Benjamin J. Wright | Peter Vollenweider | Rajesh Rawal | Susanne Lucae | Jane Worthington | Mary Susan Burnett | Alan F Wright | Per Bakke | J. Marchini | G. Abecasis | D. Rujescu | P. Muglia | C. Francks | D. Clair | H. Hakonarson | J. Vincent | Mingyao Li | D. Schlessinger | N. Samani | A. Farmer | P. McGuffin | A. Balmforth | A. Hall | J. Thompson | M. Parkes | J. Satsangi | C. Mathew | A. Dominiczak | P. Munroe | M. Caulfield | M. Farrall | A. Barton | S. Eyre | W. Thomson | Jane Worthington | A. Gulsvik | U. John | H. Völzke | P. Scheet | S. Grundy | M. Reilly | D. Rader | H. Wichmann | M. Uda | S. Wild | M. Preisig | R. Mahley | Arne S Schäfer | A. Terracciano | C. Anderson | I. Rudan | N. Wareham | V. Mooser | P. Bakke | P. Barter | R. Wilensky | H. Grabe | A. Petersmann | A. Teumer | N. Dahmen | J. Kennedy | A. Franke | A. Wright | R. McPherson | J. Kooner | I. Barroso | C. Hayward | I. Kolčić | O. Polašek | V. Vitart | H. Campbell | P. Vollenweider | G. Waeber | James F. Wilson | Jinghua Zhao | J. Chambers | L. Middleton | K. Matthews | R. Rawal | F. Busonero | R. Loos | K. Khaw | M. Burnett | S. Epstein | J. Zhao | K. Kent | A. Pichard | L. Zgaga | D. Waterworth | C. Lamina | S. Pillai | Xin Yuan | W. Berrettini | R. Waksman | Tariq Ahmad | J. Huffman | M. Wittig | Xiangjun Xiao | F. Tozzi | J. Strauss | R. Day | S. Lucae | M. Ising | L. Qu | Jason Z. Liu | J. Devaney | Susan Campbell | J. Lindsay | C. Knouff | Daniel J Rader | Marcus Ising | James L Kennedy | Ulrich John | John B Vincent | Sreekumar G Pillai | Susan Campbell | James F Wilson | Anthony J Balmforth | H-Erich Wichmann | Steve Eyre | Dawn M Waterworth | Scott Grundy | Sarah H Wild | Patricia B Munroe | Manuela Uda | Ruth J F Loos | Dan Rujescu | Mingyao Li | Alistair S Hall | Martin Preisig | Federica Tozzi | Clyde Francks | Mark Caulfield | Augusto D Pichard | Kenneth M Kent | Wade Berrettini | Richard Day | A. Kesaniemi | T. Brueckl | S. Horstmann | Lowell Satler | W. Matthai | Anna Dominiczak | John R Thompson | Xin Yuan | Jason Z Liu | Christopher W Knouff | Philip Barter | Robert Mahley | Antero Kesaniemi | Tanja Brueckl | Sonja Horstmann | Joseph M Devaney | Joseph M Lindsay | Stephen Epstein | Robert Wilensky | Hakon H Hakonarson | David St Clair | Benjamin J Wright | Stephen E. Epstein | James F. Wilson | Per S. Bakke | A. Wright | A. Barton | R. Loos | D. Schlessinger | A. Wright | Vincent Mooser | Mingyao Li | Joseph M Devaney | Paul Scheet | Andre Franke | Igor Rudan | Ruth J. F. Loos | Alan F. Wright | Jonathan Marchini | Alistair S. Hall | Joseph M. Lindsay | J. Satsangi | M. Parkes | N. Wareham | H. Grabe | A. Wright | J. Kennedy | Dan Rujescu | G. Abecasis | A. Dominiczak | Tariq Ahmad | R. Waksman | W. Berrettini | Dawn M. Waterworth | Clyde Francks | Keith Matthews | Lefkos T. Middleton | J. B. Vincent | A. Farmer | A. Barton | A. Terracciano | J. Strauss | Caroline Hayward | Peter Mcguffin | Jennifer Huffman | Norbert Dahmen | Daniel J. Rader | Martin Preisig | H. Wichmann | Inês Barroso | Philip Barter | Christopher G. Mathew | Nilesh J. Samani | P. Vollenweider | D. Rujescu | Ulrich John | G. Waeber | Sarah H. Wild | W. Thomson | Ruth McPherson | I. Rudan | H. Völzke | Carl A. Anderson | D. Clair | N. Dahmen | K. Khaw | James L. Kennedy | John R. Thompson | Robert L. Wilensky | R. Day | Inês Barroso | H. Campbell | J. Worthington | Amund Gulsvik | Scott Grundy | Robert W. Mahley | J. Vincent | Susan Campbell | Xiangjun Xiao | Gonçalo R. Abecasis | M. Preisig

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