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; Gerard Waeber; Peter Vollenweider; Martin Preisig; Nicholas J. Wareham; Jing Hua Zhao; Ruth J. F. Loos; Ines 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 Schaefer; Manuela Uda; Antonio Terracciano; Xiangjun Xiao; Fabio Busonero; Paul Scheet; David Schlessinger; David St Clair; Dan Rujescu; Goncalo R. Abecasis; Hans Joergen Grabe; Alexander Teumer; Henry Voelzke; 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

doi:10.1038/ng.572

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, Gerard Waeber, Peter Vollenweider, Martin Preisig, Nicholas J. Wareham, Jing Hua Zhao, Ruth J. F. Loos, Ines 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 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 Schaefer, Manuela Uda, Antonio Terracciano, Xiangjun Xiao, Fabio Busonero, Paul Scheet, David Schlessinger, David St Clair, Dan Rujescu, Goncalo R. Abecasis, Hans Joergen Grabe, Alexander Teumer, Henry Voelzke, 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

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Abstract

Smoking is a leading global cause of disease and mortality(1). 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 language	English
Pages (from-to)	436 - U75
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	5
DOIs	https://doi.org/10.1038/ng.572
Publication status	Published - May 2010

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Liu, J. Z., Tozzi, F., Waterworth, D. M., Pillai, S. G., Muglia, P., Middleton, L., Berrettini, W., Knouff, C. W., Yuan, X., Waeber, G., Vollenweider, P., Preisig, M., Wareham, N. J., Zhao, J. H., Loos, R. J. F., Barroso, I., Khaw, K.-T., Grundy, S., Barter, P., ... Marchini, J. (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics, 42(5), 436 - U75. https://doi.org/10.1038/ng.572

@article{3a604941c10647979bf5d29ff8ccc292,

title = "Meta-analysis and imputation refines the association of 15q25 with smoking quantity",

abstract = "Smoking is a leading global cause of disease and mortality(1). 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.",

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

year = "2010",

month = may,

doi = "10.1038/ng.572",

language = "English",

volume = "42",

pages = "436 -- U75",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Research",

number = "5",

}

Liu, JZ, Tozzi, F, Waterworth, DM, Pillai, SG, Muglia, P, Middleton, L, Berrettini, W, Knouff, CW, Yuan, X, Waeber, G, Vollenweider, P, Preisig, M, Wareham, NJ, Zhao, JH, Loos, RJF, Barroso, I, Khaw, K-T, Grundy, S, Barter, P, Mahley, R, Kesaniemi, A, McPherson, R, Vincent, JB, Strauss, J, Kennedy, JL, Farmer, A , McGuffin, P, Day, R, Matthews, K, Bakke, P, Gulsvik, A, Lucae, S, Ising, M, Brueckl, T, Horstmann, S, Wichmann, H-E, Rawal, R, Dahmen, N, Lamina, C, Polasek, O, Zgaga, L, Huffman, J, Campbell, S, Kooner, J, Chambers, JC, Burnett, MS, Devaney, JM, Pichard, AD, Kent, KM, Satler, L, Lindsay, JM, Waksman, R, Epstein, S, Wilson, JF, Wild, SH, Campbell, H, Vitart, V, Reilly, MP, Li, M, Qu, L, Wilensky, R, Matthai, W, Hakonarson, HH, Rader, DJ, Franke, A, Wittig, M, Schaefer, A, Uda, M, Terracciano, A, Xiao, X, Busonero, F, Scheet, P, Schlessinger, D, St Clair, D, Rujescu, D, Abecasis, GR, Grabe, HJ, Teumer, A, Voelzke, H, Petersmann, A, John, U, Rudan, I, Hayward, C, Wright, AF, Kolcic, I, Wright, BJ, Thompson, JR, Balmforth, AJ, Hall, AS, Samani, NJ, Anderson, CA, Ahmad, T, Mathew, CG, Parkes, M, Satsangi, J, Caulfield, M, Munroe, PB, Farrall, M, Dominiczak, A, Worthington, J, Thomson, W, Eyre, S, Barton, A, Mooser, V, Francks, C & Marchini, J 2010, 'Meta-analysis and imputation refines the association of 15q25 with smoking quantity', Nature Genetics, vol. 42, no. 5, pp. 436 - U75. https://doi.org/10.1038/ng.572

TY - JOUR

T1 - Meta-analysis and imputation refines the association of 15q25 with smoking quantity

AU - Liu, Jason Z.

AU - Tozzi, Federica

AU - Waterworth, Dawn M.

AU - Pillai, Sreekumar G.

AU - Muglia, Pierandrea

AU - Middleton, Lefkos

AU - Berrettini, Wade

AU - Knouff, Christopher W.

AU - Yuan, Xin

AU - Waeber, Gerard

AU - Vollenweider, Peter

AU - Preisig, Martin

AU - Wareham, Nicholas J.

AU - Zhao, Jing Hua

AU - Loos, Ruth J. F.

AU - Barroso, Ines

AU - Khaw, Kay-Tee

AU - Grundy, Scott

AU - Barter, Philip

AU - Mahley, Robert

AU - Kesaniemi, Antero

AU - McPherson, Ruth

AU - Vincent, John B.

AU - Strauss, John

AU - Kennedy, James L.

AU - Farmer, Anne

AU - McGuffin, Peter

AU - Day, Richard

AU - Matthews, Keith

AU - Bakke, Per

AU - Gulsvik, Amund

AU - Lucae, Susanne

AU - Ising, Marcus

AU - Brueckl, Tanja

AU - Horstmann, Sonja

AU - Wichmann, H-Erich

AU - Rawal, Rajesh

AU - Dahmen, Norbert

AU - Lamina, Claudia

AU - Polasek, Ozren

AU - Zgaga, Lina

AU - Huffman, Jennifer

AU - Campbell, Susan

AU - Kooner, Jaspal

AU - Chambers, John C.

AU - Burnett, Mary Susan

AU - Devaney, Joseph M.

AU - Pichard, Augusto D.

AU - Kent, Kenneth M.

AU - Satler, Lowell

AU - Lindsay, Joseph M.

AU - Waksman, Ron

AU - Epstein, Stephen

AU - Wilson, James F.

AU - Wild, Sarah H.

AU - Campbell, Harry

AU - Vitart, Veronique

AU - Reilly, Muredach P.

AU - Li, Mingyao

AU - Qu, Liming

AU - Wilensky, Robert

AU - Matthai, William

AU - Hakonarson, Hakon H.

AU - Rader, Daniel J.

AU - Franke, Andre

AU - Wittig, Michael

AU - Schaefer, Arne

AU - Uda, Manuela

AU - Terracciano, Antonio

AU - Xiao, Xiangjun

AU - Busonero, Fabio

AU - Scheet, Paul

AU - Schlessinger, David

AU - St Clair, David

AU - Rujescu, Dan

AU - Abecasis, Goncalo R.

AU - Grabe, Hans Joergen

AU - Teumer, Alexander

AU - Voelzke, Henry

AU - Petersmann, Astrid

AU - John, Ulrich

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Wright, Alan F.

AU - Kolcic, Ivana

AU - Wright, Benjamin J.

AU - Thompson, John R.

AU - Balmforth, Anthony J.

AU - Hall, Alistair S.

AU - Samani, Nilesh J.

AU - Anderson, Carl A.

AU - Ahmad, Tariq

AU - Mathew, Christopher G.

AU - Parkes, Miles

AU - Satsangi, Jack

AU - Caulfield, Mark

AU - Munroe, Patricia B.

AU - Farrall, Martin

AU - Dominiczak, Anna

AU - Worthington, Jane

AU - Thomson, Wendy

AU - Eyre, Steve

AU - Barton, Anne

AU - Mooser, Vincent

AU - Francks, Clyde

AU - Marchini, Jonathan

PY - 2010/5

Y1 - 2010/5

N2 - Smoking is a leading global cause of disease and mortality(1). 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.

AB - Smoking is a leading global cause of disease and mortality(1). 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.

U2 - 10.1038/ng.572

DO - 10.1038/ng.572

M3 - Article

SN - 1546-1718

VL - 42

SP - 436 - U75

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

Abstract

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