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

Liu, J. Z. et al. (2010) Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics, 42(5), pp. 436-440. (doi: 10.1038/ng.572)

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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

Item Type:Articles
Keywords:ASSOCIATION ATHEROSCLEROSIS CANCER Cohort COMMUNITY DISEASE ENGLAND GENE genes genetics GENOME-WIDE ASSOCIATION HEART INCREASE INDIVIDUALS LUNG-CANCER meta-analysis METAANALYSIS NICOTINE DEPENDENCE POPULATION PROJECT RECEPTOR RISK-FACTORS SMOKING smoking quantity SNPS SUSCEPTIBILITY LOCUS
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dominiczak, Professor Anna
Authors: 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., 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. Y., Qu, L., Wilensky, R., Matthai, W., Hakonarson, H. H., Rader, D. J., Franke, A., Wittig, M., Schafer, 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., Volzke, 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., and Marchini, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences
Journal Name:Nature Genetics
ISSN:1061-4036

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