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

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.; Barroso, I.; Khaw, K.T.; Grundy, S.; Barter, P.; Mahley, R.; Kesaniemi, A.; McPherson, R.; Vincent, J.B.; Strauss, J.; Kennedy, J.L.; 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, J.C.; Burnett, M.S.; Devaney, J.M.; Pichard, A.D.; Kent, K.M.; Satler, L.; Lindsay, J.M.; Waksman, R.; Epstein, S.; Wilson, J.F.; Wild, S.H.; Campbell, H.; Vitart, V.; Reilly, M.P.; Li, M.; Qu, L.; Wilensky, R.; Matthai, W.; Hakonarson, H.H.; Rader, D.J.; Franke, A.; Wittig, M.; Schäfer, A.; Uda, M.; Terracciano, A.; Xiao, X.; Busonero, F.; Scheet, P.; Schlessinger, D.; St Clair, D.; Rujescu, D.; Abecasis, G.R.; Grabe, H.J.; Teumer, A.; Völzke, H.; Petersmann, A.; John, U.; Rudan, I.; Hayward, C.; Wright, A.F.; Kolcic, I.; Wright, B.J.; Thompson, J.R.; Balmforth, A.J.; Hall, A.S.; Samani, N.J.; Anderson, C.A.; Ahmad, T.; Mathew, C.G.; Parkes, M.; Satsangi, J.; Caulfield, M.; Munroe, P.B.; Farrall, M.; Dominiczak, A.; Worthington, J.; Thomson, W.; Eyre, S.; Barton, A.; Mooser, V.; Francks, C.; Marchini, J.

doi:10.1038/ng.572

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

Details

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Serval ID

serval:BIB_F756B77E9388

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature Genetics

Author(s)

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., Barroso I., Khaw K.T., Grundy S., Barter P., Mahley R., Kesaniemi A., McPherson R., Vincent J.B., Strauss J., Kennedy J.L., 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 J.C., Burnett M.S., Devaney J.M., Pichard A.D., Kent K.M., Satler L., Lindsay J.M., Waksman R., Epstein S., Wilson J.F., Wild S.H., Campbell H., Vitart V., Reilly M.P., Li M., Qu L., Wilensky R., Matthai W., Hakonarson H.H., Rader D.J., Franke A., Wittig M., Schäfer A., Uda M., Terracciano A., Xiao X., Busonero F., Scheet P., Schlessinger D., St Clair D., Rujescu D., Abecasis G.R., Grabe H.J., Teumer A., Völzke H., Petersmann A., John U., Rudan I., Hayward C., Wright A.F., Kolcic I., Wright B.J., Thompson J.R., Balmforth A.J., Hall A.S., Samani N.J., Anderson C.A., Ahmad T., Mathew C.G., Parkes M., Satsangi J., Caulfield M., Munroe P.B., Farrall M., Dominiczak A., Worthington J., Thomson W., Eyre S., Barton A., Mooser V., Francks C., Marchini J.

Working group(s)

Wellcome Trust Case Control Consortium

ISSN

1546-1718 ([electronic])
1061-4036 ([linking])

Publication state

Published

Issued date

2010

Peer-reviewed

Oui

Volume

Number

Pages

436-440

Language

english

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.

Keywords

Genome-Wide Association, Nicotine Dependence, Lung-Cancer, Susceptibility Locus, Risk-Factors, Disease, Genes, SNPS, Colaus Study

URN

urn:nbn:ch:serval-BIB_F756B77E93889

OAI-PMH

oai:serval.unil.ch:BIB_F756B77E9388

DOI

10.1038/ng.572

Pubmed

20418889

Web of science

000277179500016