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  Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4

Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., et al. (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet, 43(10), 977-83. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21926972 http://www.nature.com/ng/journal/v43/n10/pdf/ng.943.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7971-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7972-8
Genre: Journal Article

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Sklar, P., Author
Ripke, S., Author
Scott, L. J., Author
Andreassen, O. A., Author
Cichon, S., Author
Craddock, N., Author
Edenberg, H. J., Author
Nurnberger, J. I., Author
Rietschel, M., Author
Blackwood, D., Author
Corvin, A., Author
Flickinger, M., Author
Guan, W., Author
Mattingsdal, M., Author
McQuillin, A., Author
Kwan, P., Author
Wienker, T. F.1, Author              
Daly, M., Author
Dudbridge, F., Author
Holmans, P. A., Author
Lin, D., AuthorBurmeister, M., AuthorGreenwood, T. A., AuthorHamshere, M. L., AuthorMuglia, P., AuthorSmith, E. N., AuthorZandi, P. P., AuthorNievergelt, C. M., AuthorMcKinney, R., AuthorShilling, P. D., AuthorSchork, N. J., AuthorBloss, C. S., AuthorForoud, T., AuthorKoller, D. L., AuthorGershon, E. S., AuthorLiu, C., AuthorBadner, J. A., AuthorScheftner, W. A., AuthorLawson, W. B., AuthorNwulia, E. A., AuthorHipolito, M., AuthorCoryell, W., AuthorRice, J., AuthorByerley, W., AuthorMcMahon, F. J., AuthorSchulze, T. G., AuthorBerrettini, W., AuthorLohoff, F. W., AuthorPotash, J. B., AuthorMahon, P. B., AuthorMcInnis, M. G., AuthorZollner, S., AuthorZhang, P., AuthorCraig, D. W., AuthorSzelinger, S., AuthorBarrett, T. B., AuthorBreuer, R., AuthorMeier, S., AuthorStrohmaier, J., AuthorWitt, S. H., AuthorTozzi, F., AuthorFarmer, A., AuthorMcGuffin, P., AuthorStrauss, J., AuthorXu, W., AuthorKennedy, J. L., AuthorVincent, J. B., AuthorMatthews, K., AuthorDay, R., AuthorFerreira, M. A., AuthorO'Dushlaine, C., AuthorPerlis, R., AuthorRaychaudhuri, S., AuthorRuderfer, D., AuthorHyoun, P. L., AuthorSmoller, J. W., AuthorLi, J.2, Author              Absher, D., AuthorThompson, R. C., AuthorMeng, F. G., AuthorSchatzberg, A. F., AuthorBunney, W. E., AuthorBarchas, J. D., AuthorJones, E. G., AuthorWatson, S. J., AuthorMyers, R. M., AuthorAkil, H., AuthorBoehnke, M., AuthorChambert, K., AuthorMoran, J., AuthorScolnick, E., AuthorDjurovic, S., AuthorMelle, I., AuthorMorken, G., AuthorGill, M., AuthorMorris, D., AuthorQuinn, E., AuthorMuhleisen, T. W., AuthorDegenhardt, F. A., AuthorMattheisen, M., Author more..
Affiliations:
1Clinical Genetics (Thomas F. Wienker), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479643              
2Systems Biology (Christoph Wierling), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479656              

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Free keywords: Alleles; Bipolar Disorder/*genetics; Calcium Channels, L-Type/*genetics/metabolism; Case-Control Studies; Databases, Genetic; Genetic Loci; Genetic Predisposition to Disease; Genome, Human; *Genome-Wide Association Study; Humans; Linkage Disequilibrium; Nuclear Proteins/*genetics/metabolism; Polymorphism, Single Nucleotide; Schizophrenia/genetics
 Abstract: We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 x 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.

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 Dates: 2011
 Publication Status: Published in print
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Title: Nat Genet
Source Genre: Journal
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Pages: - Volume / Issue: 43 (10) Sequence Number: - Start / End Page: 977 - 83 Identifier: ISSN: 1546-1718 (Electronic) 1061-4036 (Linking)