Malzahn, Dörthe

[["dc.bibliographiccitation.issue","S7"],["dc.bibliographiccitation.journal","BMC Proceedings"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Balavarca, Yesilda"],["dc.contributor.author","Lozano, Jingky P"],["dc.contributor.author","Bickeböller, Heike"],["dc.date.accessioned","2021-06-01T10:48:01Z"],["dc.date.available","2021-06-01T10:48:01Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1186/1753-6561-3-S7-S80"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12882"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85802"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1753-6561"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Tests for candidate-gene interaction for longitudinal quantitative traits measured in a large cohort"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Biological Psychiatry"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Kaestner, Anne"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Bickeboeller, Heike"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2018-11-07T09:11:08Z"],["dc.date.available","2018-11-07T09:11:08Z"],["dc.date.issued","2012"],["dc.format.extent","87S"],["dc.identifier.isi","000302466000276"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26656"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.conference","67th Annual Meeting of the Society-of-Biological-Psychiatry"],["dc.relation.eventlocation","Philadelphia, PA"],["dc.relation.issn","0006-3223"],["dc.title","Introducing ORNI, the 'Odor Recognition, Naming and Interpretation Test', a Simple and Specific Measure of Sensory-Cognitive-Emotional Processing in Schizophrenia"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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","5523"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","5533"],["dc.bibliographiccitation.volume","179"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Muppala, Vijayakumar"],["dc.contributor.author","Gehrmann, Mathias"],["dc.contributor.author","Lozano, Jingky"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Brunner, Edgar"],["dc.contributor.author","Zientkowska, Marta"],["dc.contributor.author","Herrmann, Thomas"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Dressel, Ralf"],["dc.date.accessioned","2022-06-08T07:57:36Z"],["dc.date.available","2022-06-08T07:57:36Z"],["dc.date.issued","2007"],["dc.description.abstract","The stress-inducible heat shock protein (HSP) 70 is known to function as an endogenous danger signal that can increase the immunogenicity of tumors and induce CTL responses. We show in this study that HSP70 also activates mouse NK cells that recognize stress-inducible NKG2D ligands on tumor cells. Tumor size and the rate of metastases derived from HSP70-overexpressing human melanoma cells were found to be reduced in T and B cell-deficient SCID mice, but not in SCID/beige mice that lack additionally functional NK cells. In the SCID mice with HSP70-overexpressing tumors, NK cells were activated so that they killed ex vivo tumor cells that expressed NKG2D ligands. In the tumors, the MHC class I chain-related (MIC) A and B molecules were found to be expressed. Interestingly, a counter selection was observed against the expression of MICA/B in HSP70-overexpressing tumors compared with control tumors in SCID, but not in SCID/beige mice, suggesting a functional relevance of MICA/B expression. The melanoma cells were found to release exosomes. HSP70-positive exosomes from the HSP70-overexpressing cells, in contrast to HSP70-negative exosomes from the control cells, were able to activate mouse NK cells in vitro to kill YAC-1 cells, which express NKG2D ligands constitutively, or the human melanoma cells, in which MICA/B expression was induced. Thus, HSP70 and inducible NKG2D ligands synergistically promote the activation of mouse NK cells resulting in a reduced tumor growth and suppression of metastatic disease."],["dc.identifier.doi","10.4049/jimmunol.179.8.5523"],["dc.identifier.isi","000250099400061"],["dc.identifier.pmid","17911639"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/110150"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-575"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.eissn","1550-6606"],["dc.relation.issn","0022-1767"],["dc.title","The Heat Shock Protein HSP70 Promotes Mouse NK Cell Activity against Tumors That Express Inducible NKG2D Ligands"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","487"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Genetic Epidemiology"],["dc.bibliographiccitation.lastpage","488"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Malzahn, D."],["dc.contributor.author","Neumann, A."],["dc.contributor.author","Mueller, M."],["dc.contributor.author","Wichmann, Heinz-Erich"],["dc.contributor.author","Bickeboeller, Heike"],["dc.date.accessioned","2018-11-07T11:00:59Z"],["dc.date.available","2018-11-07T11:00:59Z"],["dc.date.issued","2007"],["dc.identifier.isi","000247603700139"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51053"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.publisher.place","Hoboken"],["dc.relation.conference","15th Annual Meeting of the International-Genetic-Epidemiology-Society"],["dc.relation.eventlocation","St Petersburg, FL"],["dc.title","A non-parametric approach to detect gene-gene and gene-time interaction for longitudinal data in cohort studies"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1480"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","1502"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Isernhagen, Antje"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Viktorova, Elena"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Wermuth, Janne Marieke"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Balavarca, Yesilda"],["dc.contributor.author","Stahl-Hennig, Christiane"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Bickeboeller, Heike"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Wulf, Gerald"],["dc.contributor.author","Dressel, Ralf"],["dc.date.accessioned","2018-11-07T09:49:36Z"],["dc.date.available","2018-11-07T09:49:36Z"],["dc.date.issued","2015"],["dc.description.abstract","The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n=452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR]=0.77, P=0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR]=0.57, P=0.0400) although homozygous carriers had an increased risk to experience this complication (OR=1.92, P=0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR=0.54, P=0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon- release, and faster co-stimulation of CD8(+) T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8(+) T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.15252/emmm.201505246"],["dc.identifier.isi","000364320100008"],["dc.identifier.pmid","26483398"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12462"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35542"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/127"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","1757-4684"],["dc.relation.issn","1757-4676"],["dc.relation.workinggroup","RG Dressel"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","600"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Albrecht, Christina"],["dc.contributor.author","Brameier, Markus"],["dc.contributor.author","Hermes, Meike"],["dc.contributor.author","Ansari, Aftab A."],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Malzahn, Dörthe"],["dc.date.accessioned","2018-11-07T09:32:24Z"],["dc.date.available","2018-11-07T09:32:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Killer cell immunoglobulin-like receptors (KIR) regulate the activity of natural killer (NK) cells and have been shown to be associated with susceptibility to a number of human infectious diseases. Here, we analyzed NK cell function and genetic associations in a cohort of 52 rhesus macaques experimentally infected with SIVmac and subsequently stratified into high viral load (HVL) and low viral load (LVL) plasma viral loads at set point. This stratification coincided with fast (HVL) and slow (LVL) disease progression indicated by the disease course and critical clinical parameters including CD4+ T cell counts. HVL animals revealed sustained proliferation of NK cells but distinct loss of peripheral blood NK cell numbers and lytic function. Genetic analyses revealed that KIR genes 3DL05, 3DS05, and 3DL10 as well as 3DSW08, 3DLW03, and 3DSW09 are correlated, most likely due to underlying haplotypes. SIV-infection outcome associated with presence of transcripts for two inhibitory KIR genes (KIR3DL02, KIR3DL10) and three activating KIR genes (KIR3DSW08, KIR3DS02, KIR3DS05). Presence of KIR3DLO2 and KIR3DSW08 was associated with LVL outcome, whereas presence of KIR3DS02 was associated with HVL outcome. Furthermore, we identified epistasis between KIR and MHC class I alleles as the transcript presence of the correlated genes KIR3DL05, KIR3DS05, and KIR3DL10 increased HVL risk when Mamu-B 012 transcripts were also present or when Mamu-Al 001 transcripts were absent. These genetic associations were mirrored by changes in the numbers, the level of proliferation, and lytic capabilities of NK cells as well as overall survival time and gastro-intestinal tissue viral load."],["dc.description.sponsorship","NIH HHS [P51 OD011132]"],["dc.identifier.doi","10.3389/fimmu.2014.00600"],["dc.identifier.isi","000354531900001"],["dc.identifier.pmid","25506344"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11789"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31752"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Progression to AIDS in SIV-infected rhesus macaques is associated with distinct KIR and MHC class 1 polymorphisms and NK cell dysfunction"],["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","309"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","319"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Gerchen, Martin F."],["dc.contributor.author","Adamcio, Bartosz"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Martin, Sabine"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Radyushkin, Konstantin A."],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:44:13Z"],["dc.date.available","2017-09-07T11:44:13Z"],["dc.date.issued","2011"],["dc.description.abstract","KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution to specific schizophrenic symptoms. Using the Gottingen Research Association for Schizophrenia (GRAS) data collection of schizophrenic patients (n=1074), we performed a phenotype-based genetic association study (PGAS) of KCNN3. We show that long CAG repeats in the schizophrenic sample are specifically associated with better performance in higher cognitive tasks, comprising the capacity to discriminate, select and execute (p<0.0001). Long repeats reduce SK3 channel function, as we demonstrate by patch-clamping of transfected HEK293 cells. In contrast, modelling the opposite in mice, i.e. KCNN3 overexpression/channel hyperfunction, leads to selective deficits in higher brain functions comparable to those influenced by SK3 conductance in humans. To conclude, KCNN3 genotypes modify cognitive performance, shown here in a large sample of schizophrenic patients. Reduction of SK3 function may constitute a pharmacological target to improve cognition in schizophrenia and other conditions with cognitive impairment."],["dc.identifier.doi","10.1002/emmm.201100135"],["dc.identifier.gro","3142723"],["dc.identifier.isi","000292277600003"],["dc.identifier.pmid","21433290"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8179"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/159"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1757-4676"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A CAG repeat polymorphism of KCNN3 predicts SK3 channel function and cognitive performance in schizophrenia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S37"],["dc.bibliographiccitation.journal","Genetic Epidemiology"],["dc.bibliographiccitation.lastpage","S43"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Chen, Han"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Balliu, Brunilda"],["dc.contributor.author","Li, Cong"],["dc.contributor.author","Bailey, Julia N."],["dc.date.accessioned","2018-11-07T09:36:08Z"],["dc.date.available","2018-11-07T09:36:08Z"],["dc.date.issued","2014"],["dc.description.abstract","With the advance of next-generation sequencing technologies in recent years, rare genetic variant data have now become available for genetic epidemiology studies. For family samples, however, only a few statistical methods for association analysis of rare genetic variants have been developed. Rare variant approaches are of great interest, particularly for family data, because samples enriched for trait-relevant variants can be ascertained and rare variants are putatively enriched through segregation. To facilitate the evaluation of existing and new rare variant testing approaches for analyzing family data, Genetic Analysis Workshop 18 (GAW18) provided genotype and next-generation sequencing data and longitudinal blood pressure traits from extended pedigrees of Mexican American families from the San Antonio Family Study. Our GAW18 group members analyzed real and simulated phenotype data from GAW18 by using generalized linear mixed-effects models or principal components to adjust for familial correlation or by testing binary traits using a correction factor for familial effects. With one exception, approaches dealt with the extended pedigrees in their original state using information based on the kinship matrix or alternative genetic similarity measures. For simulated data our group demonstrated that the familybased kernel machine score test is superior in power to family-based single-marker or burden tests, except in a few specific scenarios. For real data three contributions identified significant associations. They substantially reduced the number of tests before performing the association analysis. We conclude from our real data analyses that further development of strategies for targeted testing or more focused screening of genetic variants is strongly desirable. (C) 2014 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/gepi.21823"],["dc.identifier.isi","000340610500006"],["dc.identifier.pmid","25112186"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32543"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-2272"],["dc.relation.issn","0741-0395"],["dc.title","Testing Genetic Association With Rare and Common Variants in Family Data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","150"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Infectious Diseases"],["dc.bibliographiccitation.lastpage","158"],["dc.bibliographiccitation.volume","215"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Heide, Ev-Christin"],["dc.contributor.author","Malzahn, Dörthe"],["dc.contributor.author","Perske, Christina"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2018-11-07T10:28:48Z"],["dc.date.available","2018-11-07T10:28:48Z"],["dc.date.issued","2017"],["dc.description.abstract","Background. The adaptive immune system has been considered to play a minimal role in the early host response during bacterial meningitis. Methods. We investigated the progression and outcome of pneumococcal meningitis in Rag1(-/-) mice lacking functional B and T cells by assessing overall and symptom-free survival, bacteriological and histological studies, as well as flow cytometry and measurements of proinflammatory mediators. Results. The intracerebral injection of S. pneumoniae D39 induced the recruitment of B and T cells (CD4+, gamma delta and natural killer) into the brain of wild-type mice. Mice with no functional B and T cells developed clinical symptoms and succumbed to the infection earlier than the wild-type group. In the CNS, Rag1(-/-) mice showed lower levels of interleukin 1 beta, reduced microglial proliferation, and impaired granulocyte recruitment with an earlier spread of pneumococci into the bloodstream, compared with wild-type mice. Lack of B and T cells resulted in a severe impairment of bacterial clearance in blood, spleen, and liver and an exaggerated systemic inflammatory response. Conclusions. B and T cells are important effector cells delaying the spread of pneumococci from the brain to the systemic circulation and shaping the immune response, thereby prolonging the survival of the host in the absence of antibiotic treatment."],["dc.identifier.doi","10.1093/infdis/jiw517"],["dc.identifier.isi","000397203500022"],["dc.identifier.pmid","27803171"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43504"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1537-6613"],["dc.relation.issn","0022-1899"],["dc.title","The Early Adaptive Immune Response in the Pathophysiological Process of Pneumococcal Meningitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]