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  Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder

Cichon, S., Muhleisen, T. W., Degenhardt, F. A., Mattheisen, M., Miro, X., Strohmaier, J., et al. (2011). Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. Am J Hum Genet, 88(3), 372-81. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21353194 http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=276895&_user=28761&_pii=S0002929711000188&_check=y&_origin=article&_zone=toolbar&_coverDate=11-Mar-2011&view=c&originContentFamily=serial&wchp=dGLbVlS-zSkzS&md5=219097ca4b1c9070688b18cac919d58c/1-s2.0-S0002929711000188-main.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7956-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7957-6
Genre: Journal Article

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 Creators:
Cichon, S., Author
Muhleisen, T. W., Author
Degenhardt, F. A., Author
Mattheisen, M., Author
Miro, X., Author
Strohmaier, J., Author
Steffens, M., Author
Meesters, C., Author
Herms, S., Author
Weingarten, M., Author
Priebe, L., Author
Haenisch, B., Author
Alexander, M., Author
Vollmer, J., Author
Breuer, R., Author
Schmal, C., Author
Tessmann, P., Author
Moebus, S., Author
Wichmann, H. E., Author
Schreiber, S., Author
Muller-Myhsok, B., AuthorLucae, S., AuthorJamain, S., AuthorLeboyer, M., AuthorBellivier, F., AuthorEtain, B., AuthorHenry, C., AuthorKahn, J. P., AuthorHeath, S., AuthorHamshere, M., AuthorO'Donovan, M. C., AuthorOwen, M. J., AuthorCraddock, N., AuthorSchwarz, M., AuthorVedder, H., AuthorKammerer-Ciernioch, J., AuthorReif, A., AuthorSasse, J., AuthorBauer, M., AuthorHautzinger, M., AuthorWright, A., AuthorMitchell, P. B., AuthorSchofield, P. R., AuthorMontgomery, G. W., AuthorMedland, S. E., AuthorGordon, S. D., AuthorMartin, N. G., AuthorGustafsson, O., AuthorAndreassen, O., AuthorDjurovic, S., AuthorSigurdsson, E., AuthorSteinberg, S., AuthorStefansson, H., AuthorStefansson, K., AuthorKapur-Pojskic, L., AuthorOruc, L., AuthorRivas, F., AuthorMayoral, F., AuthorChuchalin, A., AuthorBabadjanova, G., AuthorTiganov, A. S., AuthorPantelejeva, G., AuthorAbramova, L. I., AuthorGrigoroiu-Serbanescu, M., AuthorDiaconu, C. C., AuthorCzerski, P. M., AuthorHauser, J., AuthorZimmer, A., AuthorLathrop, M., AuthorSchulze, T. G., AuthorWienker, T. F.1, Author              Schumacher, J., AuthorMaier, W., AuthorPropping, P., AuthorRietschel, M., AuthorNothen, M. 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              

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Free keywords: Animals; Bipolar Disorder/*genetics; Brain/pathology; Case-Control Studies; Follow-Up Studies; *Genetic Predisposition to Disease; *Genetic Variation; *Genome-Wide Association Study; Humans; Mice; Neurocan/*genetics; Polymorphism, Single Nucleotide/genetics; Reproducibility of Results
 Abstract: We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 x 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 x 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 x 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.

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Title: Am J Hum Genet
Source Genre: Journal
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Pages: - Volume / Issue: 88 (3) Sequence Number: - Start / End Page: 372 - 81 Identifier: ISSN: 1537-6605 (Electronic) 0002-9297 (Linking)