Displaying 101 - 102 of 102
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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., Mahley, R. and 86 moreLiu, 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., 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. (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics, 42(5), 436-440. doi:10.1038/ng.572.
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. -
Muglia, P., Tozzi, F., Galwey, N. W., Francks, C., Upmanyu, R., Kong, X., Antoniades, A., Domenici, E., Perry, J., Rothen, S., Vandeleur, C. L., Mooser, V., Waeber, G., Vollenweider, P., Preisig, M., Lucae, S., Muller-Myhsok, B., Holsboer, F., Middleton, L. T., & Roses, A. D. (2010). Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts. Molecular Psychiatry, 15(6), 589-601. doi:10.1038/mp.2008.131.
Abstract
Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD. We conducted a genome-wide association study (GWAS) in two independent datasets. The first GWAS was performed on 1022 recurrent MDD patients and 1000 controls genotyped on the Illumina 550 platform. The second was conducted on 492 recurrent MDD patients and 1052 controls selected from a population-based collection, genotyped on the Affymetrix 5.0 platform. Neither GWAS identified any SNP that achieved GWAS significance. We obtained imputed genotypes at the Illumina loci for the individuals genotyped on the Affymetrix platform, and performed a meta-analysis of the two GWASs for this common set of approximately half a million SNPs. The meta-analysis did not yield genome-wide significant results either. The results from our study suggest that SNPs with substantial odds ratio are unlikely to exist for MDD, at least in our datasets and among the relatively common SNPs genotyped or tagged by the half-million-loci arrays. Meta-analysis of larger datasets is warranted to identify SNPs with smaller effects or with rarer allele frequencies that contribute to the risk of MDD.Additional information
http://www.nature.com/mp/journal/v15/n6/suppinfo/mp2008131s1.html?url=/mp/journ…
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