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 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 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

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, 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

Applied Medicine

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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.

Original language	English
Pages (from-to)	436-440
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	5
Early online date	25 Apr 2010
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., ... Wellcome Trust Case Control Consortium (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics, 42(5), 436-440. https://doi.org/10.1038/ng.572

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, SE, Kooner, J, Chambers, JC, Burnett, MS, Devaney, JM, Pichard, AD, Kent, KM, St Clair, DM & Wellcome Trust Case Control Consortium 2010, 'Meta-analysis and imputation refines the association of 15q25 with smoking quantity', Nature Genetics, vol. 42, no. 5, pp. 436-440. https://doi.org/10.1038/ng.572

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

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.",

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 G{\'e}rard Waeber and Peter Vollenweider and Martin Preisig and Wareham, {Nicholas J.} and Zhao, {Jing Hua} and Loos, {Ruth J. F.} and In{\^e}s 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 Campbell, {Susan E.} and Jaspal Kooner and Chambers, {John C.} and Burnett, {Mary Susan} and Devaney, {Joseph M.} and Pichard, {Augusto D.} and Kent, {Kenneth M.} and {St Clair}, {David M.} and {Wellcome Trust Case Control Consortium}",

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AU - Muglia, Pierandrea

AU - Middleton, Lefkos

AU - Berrettini, Wade

AU - Knouff, Christopher W.

AU - Yuan, Xin

AU - Waeber, Gérard

AU - Vollenweider, Peter

AU - Preisig, Martin

AU - Wareham, Nicholas J.

AU - Zhao, Jing Hua

AU - Loos, Ruth J. F.

AU - Barroso, Inês

AU - Khaw, Kay-Tee

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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 E.

AU - Kooner, Jaspal

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AU - Wellcome Trust Case Control Consortium

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AB - 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.

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EP - 440

JO - Nature Genetics

JF - Nature Genetics

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ER -

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

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