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dc.contributor.authorHammer, C
dc.contributor.authorCichon, S
dc.contributor.authorMühleisen, T W
dc.contributor.authorHaenisch, B
dc.contributor.authorDegenhardt, F
dc.contributor.authorBreuer, R
dc.contributor.authorWitt, S H
dc.contributor.authorStrohmaier, J
dc.contributor.authorOruc, L
dc.contributor.authorRivas, F
dc.contributor.authorBabadjanova, G
dc.contributor.authorGrigoroiu-Serbanescu, M
dc.contributor.authorRöth, R
dc.contributor.authorRappold, G
dc.contributor.authorRietschel, M
dc.contributor.authorNöthen, M M
dc.contributor.authorNiesler, B
dc.contributor.authorMattheisen, Manuel
dc.contributor.authorHauser, J
dc.date.accessioned2012-10-22T17:07:10Z
dc.date.issued2012
dc.identifier.citationHammer, C, S Cichon, T W Mühleisen, B Haenisch, F Degenhardt, M Mattheisen, R Breuer, et al. 2012. Replication of functional serotonin receptor type 3A and B variants in bipolar affective disorder: A European Multicenter Study. Translational Psychiatry 2(4): e103.en_US
dc.identifier.issn2158-3188en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:9793861
dc.description.abstractSerotonin type 3 receptors (\(5-HT_3\)) are involved in learning, cognition and emotion, and have been implicated in various psychiatric phenotypes. However, their contribution to the pathomechanism of these disorders remains elusive. Three single nucleotide polymorphisms (SNPs) in the \(HTR3A\) and \(HTR3B\) genes (rs1062613, rs1176744 and rs3831455) have been associated with bipolar affective disorder (BPAD) in pilot studies, and all of them are of functional relevance. We performed a European multicenter study to confirm previous results and provide further evidence for the relevance of these SNPs to the etiology of neuropsychiatric disorders. This involved analysis of the distribution of the three SNPs among 1804 BPAD cases and 2407 healthy controls. A meta-analysis revealed a pooled odds ratio of 0.881 (P=0.009, 95% confidence intervals=0.802–0.968) for the non-synonymous functional SNP \(HTR3B\) p.Y129S (rs1176744), thereby confirming previous findings. In line with this, the three genome-wide association study samples BOMA (Bonn-Mannheim)-BPAD, WTCCC (Wellcome Trust Case Control Consortium)-BPAD and GAIN (Genetic Association Information Network)-BPAD, including >3500 patients and 5200 controls in total, showed an overrepresentation of the p.Y129 in patients. Remarkably, the meta-analysis revealed a P-value of 0.048 (OR=0.934, fixed effect model). We also performed expression analyses to gain further insights into the distribution of \(HTR3A\) and \(HTR3B\) mRNA in the human brain. \(HTR3A\) and \(HTR3B\) were detected in all investigated brain tissues with the exception of the cerebellum, and large differences in the A:B subunit ratio were observed. Interestingly, expression of the B subunit was most prominent in the brain stem, amygdalae and frontal cortex, regions of relevance to psychiatric disorders. In conclusion, the present study provides further evidence for the presence of impaired \(5-HT_3\) receptor function in BPAD.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/tp.2012.30en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337070/pdf/en_US
dash.licenseLAA
dc.subjectassociationen_US
dc.subjectbipolaren_US
dc.subjectBPADen_US
dc.subjectHTR3en_US
dc.subjectHTR3Ben_US
dc.subject5-HT3en_US
dc.titleReplication of Functional Serotonin Receptor Type 3A and B Variants in Bipolar Affective Disorder: A European Multicenter Studyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalTranslational Psychiatryen_US
dash.depositing.authorMattheisen, Manuel
dc.date.available2012-10-22T17:07:10Z
dc.identifier.doi10.1038/tp.2012.30*
dash.authorsorderedfalse
dash.contributor.affiliatedMattheisen, Manuel


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