Falkai, Peter Gaston

[["dc.bibliographiccitation.firstpage","879"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Archives of General Psychiatry"],["dc.bibliographiccitation.lastpage","888"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malzahn, Dörte"],["dc.contributor.author","Krampe, Henning"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Radyushkin, Konstantin"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Hannke, Kathrin"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Schwerdtfeger, Dayana"],["dc.contributor.author","Thanhäuser, Ivonne"],["dc.contributor.author","Gerchen, Martin Fungisai"],["dc.contributor.author","Ghorbani, Mohammed"],["dc.contributor.author","Gutwinski, Stefan"],["dc.contributor.author","Hilmes, Constanze"],["dc.contributor.author","Leppert, Richard"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Sowislo, Julia"],["dc.contributor.author","Stawicki, Sabina"],["dc.contributor.author","Stödtke, Maren"],["dc.contributor.author","Szuszies, Christoph"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Eckstein, Fritz"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:57Z"],["dc.date.available","2017-09-07T11:46:57Z"],["dc.date.issued","2010"],["dc.description.abstract","Context: Schizophrenia is the collective term for a heterogeneous group of mental disorders with a still obscure biological basis. In particular, the specific contribution of risk or candidate gene variants to the complex schizophrenic phenotype is largely unknown. Objective: To prepare the ground for a novel “phenomics” approach, a unique schizophrenia patient database was established by GRAS (Göttingen Research Association for Schizophrenia), designed to allow association of genetic information with quantifiable phenotypes. Because synaptic dysfunction plays a key role in schizophrenia, the complexin 2 gene (CPLX2) was examined in the first phenotype-based genetic association study (PGAS) of GRAS. Design: Subsequent to a classic case-control approach, we analyzed the contribution of CPLX2 polymorphisms to discrete cognitive domains within the schizophrenic population. To gain mechanistic insight into how certain CPLX2 variants influence gene expression and function, peripheral blood mononuclear cells of patients, Cplxnull mutantmice, and transfected cells were investigated.Setting: Coordinating research center (Max Planck Institute of Experimental Medicine) and 23 collaboratingpsychiatric centers all over Germany.Participants: One thousand seventy-one patients with schizophrenia (DSM-IV) examined by an invariant investigator team, resulting in the GRAS database with more than 3000 phenotypic data points per patient, and 1079 healthy control subjects of comparable ethnicity.Main Outcome Measure: Cognitive performance including executive functioning, reasoning, and verbal learning/memory. Results: Six single-nucleotide polymorphisms, distributed over the whole CPLX2 gene, were found to be highly associated with current cognition of schizophrenic subjects but only marginally with premorbid intelligence. Correspondingly, in Cplx2-null mutant mice, prominent cognitive loss of function was obtained only in combination with a minor brain lesion applied during puberty, modeling a clinically relevant environmental risk (“second hit”) for schizophrenia. In the human CPLX2 gene, 1 of the identified 6 cognition-relevant single-nucleotide polymorphisms, rs3822674 in the 3´ untranslated region, was detected to influence microRNA-498 binding and gene expression. The same marker was associated with differential expression of CPLX2 in peripheral blood mononuclear cells. Conclusions: The PGAS allows identification of markerassociated clinical/biological traits. Current cognitive performance in schizophrenic patients is modified by CPLX2 variants modulating posttranscriptional gene expression"],["dc.identifier.doi","10.1001/archgenpsychiatry.2010.107"],["dc.identifier.fs","577608"],["dc.identifier.gro","3150567"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6097"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7343"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","final"],["dc.rights.access","closedAccess"],["dc.subject","Schizophrenia"],["dc.subject.ddc","610"],["dc.title","Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","89"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Revista de psiquiatria clínica"],["dc.bibliographiccitation.lastpage","96"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Schmitt, Andrea"],["dc.contributor.author","Otto, Sylvia"],["dc.contributor.author","Jatzko, Alexander"],["dc.contributor.author","Ruf, Matthias"],["dc.contributor.author","Demirakca, Traute"],["dc.contributor.author","Tost, Heike"],["dc.contributor.author","Gruber, Oliver"],["dc.contributor.author","Parlapani, Eleni"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Braus, Dieter F."],["dc.date.accessioned","2018-11-07T08:35:29Z"],["dc.date.available","2018-11-07T08:35:29Z"],["dc.date.issued","2009"],["dc.description.abstract","Objectives: In first-episode schizophrenia patients, functional magnetic resonance imaging (fMRI) has shown prefronto-parietal dysfunction during acoustic and visual stimulation. The aim of this study was to investigate the prefronto-parietal network in elderly schizophrenia patients using the same paradigm. Additionally, we hypothesized favourable effects on brain activation by the atypical antipsychotic clozapine compared to typical neuroleptics. Methods: We investigated 18 elderly, chronic schizophrenia patients and 21 elderly healthy controls. Nine schizophrenia patients had been medicated with clozapine and 9 had been receiving typical neuroleptics over decades. In addition to assessments with psychopathological and neuropsychological rating scales we used an acoustic and visual stimulation paradigm in a 1.5 Tesla MRI scanner to investigate BOLD-response in different brain areas. Results: Compared to healthy controls schizophrenia patients showed decreased brain activation in the prefrontal and parietal cortex as well as medial anterior cingulate gyrus compared to healthy controls. In these regions, patients medicated with clozapine showed increased BOLD-response compared to patients treated with typical neuroleptics. Discussion: Our study confirmed prefronto-parietal network disturbances in elderly schizophrenia patients thus pointing to the preservation of brain activation deficits and the influence of neurodevelopmental disturbances in chronic schizophrenia until old-age. Conclusion: The atypical antipsychotic clozapine seems to facilitate brain activation even in elderly, chronic schizophrenia patients."],["dc.identifier.doi","10.1590/S0101-60832009000300002"],["dc.identifier.fs","548703"],["dc.identifier.isi","000269276800002"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5793"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18078"],["dc.language.iso","es"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Univ Sao Paulo, Inst Psiquiatria"],["dc.relation.issn","0101-6083"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Parieto-prefrontal dysfunction during visuo-auditory information processing in elderly, chronic schizophrenic patients and medication effects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1651"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","1659"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Kessler, Holger"],["dc.contributor.author","Pajonk, Frank-Gerald"],["dc.contributor.author","Bach, Daniela"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Herrmann, Wolfgang"],["dc.contributor.author","Multhaup, Gerd"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Schäfer, Stephanie"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas"],["dc.date.accessioned","2019-07-09T11:52:23Z"],["dc.date.available","2019-07-09T11:52:23Z"],["dc.date.issued","2008"],["dc.description.abstract","A plethora of reports suggest that copper (Cu) homeostasis is disturbed in Alzheimer’s disease (AD). In the present report we evaluated the efficacy of oral Cu supplementation on Cp. biomarkers for AD. In a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial (12 months long) patients with mild AD received either Cu-(II)-orotate-dihydrate (verum group; 8 mg Cu daily) or placebo (placebo group). The primary outcome measures in CSF were Aβ42, Tau and Phospho-Tau. The clinical trial demonstrates that long-term oral intake of 8 mg Cu can be excluded as a risk factor for AD based on CSF biomarker analysis. Cu intake had no effect on the progression of Tau and Phospho-Tau levels in CSF. While Aβ42 levels declined by 30% in the placebo group (P = 0.001), they decreased only by 10% (P = 0.04) in the verum group. Since decreased CSF Aβ42 is a diagnostic marker for AD, this observation may indicate that Cu treatment had a positive effect on a relevant AD biomarker. Using mini-mental state examination (MMSE) and Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) we have previously demonstrated that there are no Cu treatment effects on cognitive performance, however. Finally, CSF Aβ42 levels declined significantly in both groups within 12 months supporting the notion that CSF Aβ42 may be valid not only for diagnostic but also for prognostic purposes in AD."],["dc.identifier.doi","10.1007/s00702-008-0136-2"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60172"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Springer"],["dc.publisher.place","Vienna"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Effect of copper intake on CSF parameters in patients with mild Alzheimer’s disease: a pilot phase 2 clinical trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","311"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","European Archives of Psychiatry and Clinical Neuroscience"],["dc.bibliographiccitation.lastpage","312"],["dc.bibliographiccitation.volume","261"],["dc.contributor.author","Möller, H.-J."],["dc.contributor.author","Falkai, P."],["dc.date.accessioned","2019-07-09T11:53:13Z"],["dc.date.available","2019-07-09T11:53:13Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1007/s00406-011-0221-7"],["dc.identifier.fs","583456"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7123"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60368"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Springer"],["dc.publisher.place","Berlin/Heidelberg"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Pain, affect and psychotic illness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","133"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","ARCH GEN PSYCHIATRY"],["dc.bibliographiccitation.lastpage","143"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Pajonk, Frank-Gerald"],["dc.contributor.author","Wobrock, Thomas"],["dc.contributor.author","Gruber, Oliver"],["dc.contributor.author","Scherk, Harald"],["dc.contributor.author","Berner, Dorothea"],["dc.contributor.author","Kaizl, Inge"],["dc.contributor.author","Kierer, Astrid"],["dc.contributor.author","Müller, Stephanie"],["dc.contributor.author","Oest, Martin"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Backens, Martin"],["dc.contributor.author","Schneider-Axmann, Thomas"],["dc.contributor.author","Thornton, Allen E."],["dc.contributor.author","Honer, Willam G."],["dc.contributor.author","Falkai, Peter"],["dc.date.accessioned","2019-07-10T08:13:32Z"],["dc.date.available","2019-07-10T08:13:32Z"],["dc.date.issued","2010"],["dc.description.abstract","Context: Hippocampal volume is lower than expected in patients with schizophrenia; however, whether this represents a fixed deficit is uncertain. Exercise is a stimulus to hippocampal plasticity. Objective: To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness. Design: Randomized controlled study. Setting: Patients attending a day hospital program or an outpatient clinic. Patients or Other Participants: Male patients with chronic schizophrenia and matched healthy subjects. Interventions: Aerobic exercise training (cycling) and playing table football (control group) for a period of 3 months. Main Outcome Measures: Magnetic resonance imaging of the hippocampus. Secondary outcome measures were magnetic resonance spectroscopy, neuropsychological (Rey Auditory Verbal Learning Test, Corsi blocktapping test), and clinical (Positive and Negative Syndrome Scale) features. Results: Following exercise training, relative hippocampal volume increased significantly in patients (12%) and healthy subjects (16%), with no change in the nonexercise group of patients (−1%). Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption (r=0.71; P=.003). In the schizophrenia exercise group (but not the controls), change in hippocampal volume was associated with a 35% increase in the N-acetylaspartate to creatine ratio in the hippocampus. Finally, improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume (r=0.51; P .05). Conclusion: These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise."],["dc.identifier.fs","575536"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6145"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61270"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Hippocampal Plasticity in Response to Exercise in Schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","72"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal für Neuologie, Neurochirurgie und Psychiatrie"],["dc.bibliographiccitation.lastpage","76"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schmitt, Andrea"],["dc.contributor.author","Falkai, Peter Gaston"],["dc.contributor.author","Parlapani, Eleni"],["dc.date.accessioned","2019-07-10T08:13:30Z"],["dc.date.available","2019-07-10T08:13:30Z"],["dc.date.issued","2009"],["dc.description.abstract","Bei Schizophrenie finden sich Volumenverminderungen der grauen Substanz, besonders im Hippokampus und präfrontalen Kortex, sowie erweiterte Seitenventrikel. Die Diagnose dieser strukturellen Veränderungen sowie eine Hypergyrifizierung schon bei Ersterkrankung sprechen für das Vorliegen einer neuronalen Entwicklungsstörung, während andererseits die Volumenabnahme der grauen Substanz während der Erkrankungsdauer für einen zusätzlichen neurodegenerativen Prozess spricht. Klassische Anzeichen eines neurodegenerativen Prozesses wie die Abnahme der Neuronenzahl oder eine Astrogliose liegen bei der Erkrankung nicht gesichert vor. Dagegen gibt es Hinweise auf verminderte synaptische Proteine, die zu einer Konnektivitätsstörung in einem neuronalen Netzwerk führen können. Zusätzlich wurde in einer kürzlich veröffentlichten Postmortem- Studie eine verminderte Anzahl proliferierender Stammzellen im Gyrus dentatus des Hippokampus bei schizophrenen Patienten gefunden. Dies könnte eine zusätzliche Rolle bei der Bildung des Volumenverlusts des Hippokam- Aus der Abteilung für Psychiatrie und Psychotherapie, Universität Göttingen Korrespondenzadresse: Dr. med. Andrea Schmitt, Abteilung für Psychiatrie und Psychotherapie, Universität Göttingen, D-37075 Göttingen, von-Siebold-Straße 5; E-Mail: aschmit@gwdg.de pus spielen. Welche Wirkung dabei antipsychotisch wirksame Medikamente spielen, ist bislang unklar. Auch genetische Risikofaktoren können eine Rolle bei strukturellen Veränderungen im Gehirn spielen. Nachgewiesen wurde das für den Neuregulin-1-Risikohaplotyp (HAPICE), der bei schizophrenen Patienten und ihren gesunden Angehörigen mit einem kleineren Hippokampusvolumen assoziiert war. Weitere Erkenntnisse über Risikofaktoren der Schizophrenie könnten zukünftig spezifischere Therapieoptionen ermöglichen."],["dc.description.abstract","In schizophrenia, a reduced volume of gray matter, especially in the hippocampus and the prefrontal cortex, as well as enlarged lateral ventricles can be found. The diagnosis of these structural changes plus hypergyrification already in first-episode disease argues for the existence of a neuronal developmental disorder. On the other hand, the volume reduction of gray matter in the course of the illness additionally indicates progressing neurodegeneration. Indeed, classical signs of a neurodegenerative process such as reduction of neurons or astrogliosis cannot be securely identified for the disease, whereas there is evidence for reduced synaptic proteins which may lead to disturbed connectivity in a neuronal network. A recently published post-mortem study accessorily reports a reduced number of proliferating stem cells in the gyrus dentatus of the hippocampus in schizophrenic patients which might add to hippocampal volume loss. At present, the effects of antipsychotic medication remain unexplained. Genetic risk factors should also be considered as a possible cause for structural alterations in the brain. The neuregulin-1 risk haplotype (HAPICE), for example, has been proven to be associated with reduced hippocampus volume in schizophrenic patients and their healthy relatives. Further insights into schizophrenia risk factors could prospectively facilitate specific therapeutic options."],["dc.identifier.fs","535919"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6035"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61264"],["dc.language.iso","de"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1608-1587"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Ist die Schizophrenie eine Störung der Synapto- oder Neurogenese?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","156"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology"],["dc.bibliographiccitation.lastpage","170"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Budde, Monika"],["dc.contributor.author","Friedrichs, Stefanie"],["dc.contributor.author","Alliey-Rodriguez, Ney"],["dc.contributor.author","Ament, Seth"],["dc.contributor.author","Badner, Judith A."],["dc.contributor.author","Berrettini, Wade H."],["dc.contributor.author","Bloss, Cinnamon S."],["dc.contributor.author","Byerley, William"],["dc.contributor.author","Cichon, Sven"],["dc.contributor.author","Comes, Ashley L."],["dc.contributor.author","Coryell, William"],["dc.contributor.author","Craig, David W."],["dc.contributor.author","Degenhardt, Franziska"],["dc.contributor.author","Edenberg, Howard J."],["dc.contributor.author","Foroud, Tatiana"],["dc.contributor.author","Forstner, Andreas J."],["dc.contributor.author","Frank, Josef"],["dc.contributor.author","Gershon, Elliot S."],["dc.contributor.author","Goes, Fernando S."],["dc.contributor.author","Greenwood, Tiffany A."],["dc.contributor.author","Guo, Yiran"],["dc.contributor.author","Hipolito, Maria"],["dc.contributor.author","Hood, Leroy"],["dc.contributor.author","Keating, Brendan J."],["dc.contributor.author","Koller, Daniel L."],["dc.contributor.author","Lawson, William B."],["dc.contributor.author","Liu, Chunyu"],["dc.contributor.author","Mahon, Pamela B."],["dc.contributor.author","McInnis, Melvin G."],["dc.contributor.author","McMahon, Francis J."],["dc.contributor.author","Meier, Sandra M."],["dc.contributor.author","Mühleisen, Thomas W."],["dc.contributor.author","Murray, Sarah S."],["dc.contributor.author","Nievergelt, Caroline M."],["dc.contributor.author","Nurnberger, John I."],["dc.contributor.author","Nwulia, Evaristus A."],["dc.contributor.author","Potash, James B."],["dc.contributor.author","Quarless, Danjuma"],["dc.contributor.author","Rice, John"],["dc.contributor.author","Roach, Jared C."],["dc.contributor.author","Scheftner, William A."],["dc.contributor.author","Schork, Nicholas J."],["dc.contributor.author","Shekhtman, Tatyana"],["dc.contributor.author","Shilling, Paul D."],["dc.contributor.author","Smith, Erin N."],["dc.contributor.author","Streit, Fabian"],["dc.contributor.author","Strohmaier, Jana"],["dc.contributor.author","Szelinger, Szabolcs"],["dc.contributor.author","Treutlein, Jens"],["dc.contributor.author","Witt, Stephanie H."],["dc.contributor.author","Zandi, Peter P."],["dc.contributor.author","Zhang, Peng"],["dc.contributor.author","Zöllner, Sebastian"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Falkai, Peter G."],["dc.contributor.author","Kelsoe, John R."],["dc.contributor.author","Nöthen, Markus M."],["dc.contributor.author","Rietschel, Marcella"],["dc.contributor.author","Schulze, Thomas G."],["dc.contributor.author","Malzahn, Dörthe"],["dc.date.accessioned","2019-07-09T11:50:26Z"],["dc.date.available","2019-07-09T11:50:26Z"],["dc.date.issued","2019-"],["dc.description.abstract","Genome-wide association studies of case-control status have advanced the understanding of the genetic basis of psychiatric disorders. Further progress may be gained by increasing sample size but also by new analysis strategies that advance the exploitation of existing data, especially for clinically important quantitative phenotypes. The functionally-informed efficient region-based test strategy (FIERS) introduced herein uses prior knowledge on biological function and dependence of genotypes within a powerful statistical framework with improved sensitivity and specificity for detecting consistent genetic effects across studies. As proof of concept, FIERS was used for the first genome-wide single nucleotide polymorphism (SNP)-based investigation on bipolar disorder (BD) that focuses on an important aspect of disease course, the functional outcome. FIERS identified a significantly associated locus on chromosome 15 (hg38: chr15:48965004 - 49464789 bp) with consistent effect strength between two independent studies (GAIN/TGen: European Americans, BOMA: Germans; n = 1592 BD patients in total). Protective and risk haplotypes were found on the most strongly associated SNPs. They contain a CTCF binding site (rs586758); CTCF sites are known to regulate sets of genes within a chromatin domain. The rs586758 - rs2086256 - rs1904317 haplotype is located in the promoter flanking region of the COPS2 gene, close to microRNA4716, and the EID1, SHC4, DTWD1 genes as plausible biological candidates. While implication with BD is novel, COPS2, EID1, and SHC4 are known to be relevant for neuronal differentiation and function and DTWD1 for psychopharmacological side effects. The test strategy FIERS that enabled this discovery is equally applicable for tag SNPs and sequence data."],["dc.identifier.doi","10.1016/j.euroneuro.2018.10.005"],["dc.identifier.pmid","30503783"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15939"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59772"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1873-7862"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Efficient region-based test strategy uncovers genetic risk factors for functional outcome in bipolar disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]