Search

Your search keyword '"Freitag, C M"' showing total 5 results
Start Over Author "Freitag, C M" Topic schizophrenia
5 results on '"Freitag, C M"'

1. Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.

Author

Chiocchetti AG, Haslinger D, Stein JL, de la Torre-Ubieta L, Cocchi E, Rothämel T, Lindlar S, Waltes R, Fulda S, Geschwind DH, and Freitag CM

Subjects
Algorithms, Brain growth & development, Cell Line, Tumor, Gene Regulatory Networks, Genetic Predisposition to Disease, Humans, Machine Learning, Neuronal Plasticity genetics, RNA, Messenger metabolism, Regression Analysis, Autism Spectrum Disorder genetics, Fragile X Syndrome genetics, Gene Expression Regulation, Developmental, Intellectual Disability genetics, Neurogenesis genetics, Schizophrenia genetics, Transcriptome
Abstract

Genes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders.

Published
2016
Full Text
View/download PDF

2. Common variant at 16p11.2 conferring risk of psychosis.

Author

Steinberg S, de Jong S, Mattheisen M, Costas J, Demontis D, Jamain S, Pietiläinen OP, Lin K, Papiol S, Huttenlocher J, Sigurdsson E, Vassos E, Giegling I, Breuer R, Fraser G, Walker N, Melle I, Djurovic S, Agartz I, Tuulio-Henriksson A, Suvisaari J, Lönnqvist J, Paunio T, Olsen L, Hansen T, Ingason A, Pirinen M, Strengman E, Hougaard DM, Orntoft T, Didriksen M, Hollegaard MV, Nordentoft M, Abramova L, Kaleda V, Arrojo M, Sanjuán J, Arango C, Etain B, Bellivier F, Méary A, Schürhoff F, Szoke A, Ribolsi M, Magni V, Siracusano A, Sperling S, Rossner M, Christiansen C, Kiemeney LA, Franke B, van den Berg LH, Veldink J, Curran S, Bolton P, Poot M, Staal W, Rehnstrom K, Kilpinen H, Freitag CM, Meyer J, Magnusson P, Saemundsen E, Martsenkovsky I, Bikshaieva I, Martsenkovska I, Vashchenko O, Raleva M, Paketchieva K, Stefanovski B, Durmishi N, Pejovic Milovancevic M, Lecic Tosevski D, Silagadze T, Naneishvili N, Mikeladze N, Surguladze S, Vincent JB, Farmer A, Mitchell PB, Wright A, Schofield PR, Fullerton JM, Montgomery GW, Martin NG, Rubino IA, van Winkel R, Kenis G, De Hert M, Réthelyi JM, Bitter I, Terenius L, Jönsson EG, Bakker S, van Os J, Jablensky A, Leboyer M, Bramon E, Powell J, Murray R, Corvin A, Gill M, Morris D, O'Neill FA, Kendler K, Riley B, Craddock N, Owen MJ, O'Donovan MC, Thorsteinsdottir U, Kong A, Ehrenreich H, Carracedo A, Golimbet V, Andreassen OA, Børglum AD, Mors O, Mortensen PB, Werge T, Ophoff RA, Nöthen MM, Rietschel M, Cichon S, Ruggeri M, Tosato S, Palotie A, St Clair D, Rujescu D, Collier DA, Stefansson H, and Stefansson K

Subjects
Adult, Aged, Aged, 80 and over, Bipolar Disorder complications, Bipolar Disorder epidemiology, Europe, Female, Gene Expression Profiling, Genome-Wide Association Study, Genotype, Humans, International Cooperation, Male, Middle Aged, Odds Ratio, Oligonucleotide Array Sequence Analysis, Risk Factors, Schizophrenia complications, Schizophrenia epidemiology, Young Adult, Bipolar Disorder genetics, Chromosome Aberrations, Chromosomes, Human, Pair 16 genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Schizophrenia genetics
Abstract

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Published
2014
Full Text
View/download PDF

3. The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: further evidence and meta-analysis.

Author

Weber H, Klamer D, Freudenberg F, Kittel-Schneider S, Rivero O, Scholz CJ, Volkert J, Kopf J, Heupel J, Herterich S, Adolfsson R, Alttoa A, Post A, Grußendorf H, Kramer A, Gessner A, Schmidt B, Hempel S, Jacob CP, Sanjuán J, Moltó MD, Lesch KP, Freitag CM, Kent L, and Reif A

Subjects
Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Animals, Computational Biology, Genetic Predisposition to Disease, Humans, Nitric Oxide metabolism, Nitric Oxide Synthase Type I genetics, Nitric Oxide Synthase Type I metabolism, Polymorphism, Single Nucleotide genetics, Promoter Regions, Genetic genetics, Schizophrenia genetics, Glutamic Acid metabolism, Nitric Oxide genetics, Prefrontal Cortex pathology, Schizophrenia pathology, Signal Transduction genetics, Synapses metabolism
Abstract

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia., (© 2013 Published by Elsevier B.V. and ECNP.)

Published
2014
Full Text
View/download PDF

4. DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in schizophrenic patients--support for the glutamate hypothesis of schizophrenias.

Author

Fallgatter AJ, Ehlis AC, Herrmann MJ, Hohoff C, Reif A, Freitag CM, and Deckert J

Subjects
Adult, Dysbindin, Dystrophin-Associated Proteins, Electroencephalography, Female, Genetic Predisposition to Disease genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Schizophrenia physiopathology, Brain Mapping, Carrier Proteins genetics, Evoked Potentials genetics, Prefrontal Cortex physiopathology, Schizophrenia genetics
Abstract

Dysbindin (DTNBP1) is a recently characterized protein that seems to be involved in the modulation of glutamatergic neurotransmission in the human brain, thereby influencing prefrontal cortex function and associated cognitive processes. While association, neuroanatomical and cellular studies indicate that DTNBP1 might be one of several susceptibility genes for schizophrenia, the effect of dysbindin on prefrontal brain function at an underlying neurophysiological level has not yet been explored for these patients. The NoGo-anteriorization (NGA) is a topographical event-related potential measure, which has been established as a valid neurophysiological marker of prefrontal brain function. In the present study, we investigated the influence of seven dysbindin gene variants on the NGA in a group of 44 schizophrenic patients. In line with our a priori hypothesis, one DTNBP1 polymorphism previously linked to schizophrenia (rs2619528) was found to be associated with changes in the NGA; however, the direction of this association directly contrasts with our previous findings in a healthy control sample. This differential impact of DTNBP1 gene variation on prefrontal functioning in schizophrenic patients vs. healthy controls is discussed in terms of abnormal glutamatergic baseline levels in patients suffering from schizophrenic illnesses. This is the first report on a role of DTNBP1 gene variation for prefrontal functioning at a basic neurophysiological level in schizophrenic patients. An impact on fundamental processes of cognitive response control may be one mechanism by which DTNBP1 gene variants via glutamatergic transmission contribute to the pathophysiology underlying schizophrenic illnesses.

Published
2010
Full Text
View/download PDF

5. Common variant at 16p11.2 conferring risk of psychosis

Author

Steinberg, S., de Jong, S., Sigurdsson, E., Murray, R., Corvin, A., Gill, M., Morris, D., O'Neill, F. A., Kendler, K., Riley, B., 2, Wellcome Trust Case Control Consortium, Craddock, N., Owen, M. J., Vassos, E., O'Donovan, M. C., Thorsteinsdottir, U., Kong, A., Ehrenreich, H., Carracedo, A., Golimbet, V., Andreassen, O. A., Børglum, A. D., Mors, O., Mortensen, P. B., Giegling, I., Werge, T., Ophoff, R. A., Nöthen, M. M., Rietschel, M., Cichon, S., Ruggeri, M., Tosato, S., Palotie, A., St Clair, D., Rujescu, D., Breuer, R., Collier, D. A., Stefansson, H., Stefansson, K., Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Fraser, G., Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Walker, N., Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris C A, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Melle, I., Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Djurovic, S., Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Agartz, I., Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Tuulio-Henriksson, A., Mattheisen, M., Suvisaari, J., Lönnqvist, J., Paunio, T., Olsen, L., Hansen, T., Ingason, A., Pirinen, M., Strengman, E., GROUP, Hougaard, D. M., Costas, J., Orntoft, T., Didriksen, M., Hollegaard, M. V., Nordentoft, M., Abramova, L., Kaleda, V., Arrojo, M., Sanjuán, J., Arango, C., Etain, B., Demontis, D., Bellivier, F., Méary, A., Schürhoff, F., Szoke, A., Ribolsi, M., Magni, V., Siracusano, A., Sperling, S., Rossner, M., Christiansen, C., Jamain, S., Kiemeney, L. A., Franke, B., van den Berg, L. H., Veldink, J., Curran, S., Bolton, P., Poot, M., Staal, W., Rehnstrom, K., Kilpinen, H., Pietiläinen, O. P. H., Freitag, C. M., Meyer, J., Magnusson, P., Saemundsen, E., Martsenkovsky, I., Bikshaieva, I., Martsenkovska, I., Vashchenko, O., Raleva, M., Paketchieva, K., Lin, K., Stefanovski, B., Durmishi, N., Pejovic Milovancevic, M., Lecic Tosevski, D., Silagadze, T., Naneishvili, N., Mikeladze, N., Surguladze, S., Vincent, J. B., Farmer, A., Papiol, S., Mitchell, P. B., Wright, A., Schofield, P. R., Fullerton, J. M., Montgomery, G. W., Martin, N. G., Rubino, I. A., van Winkel, R., Kenis, G., De Hert, M., Huttenlocher, J., Réthelyi, J. M., Bitter, I., Terenius, L., Jönsson, E. G., Bakker, S., van Os, J., Jablensky, A., Leboyer, M., Bramon, E., Powell, J., deCODE Genet, IS-101 Reykjavik, Iceland Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA Univ Bonn, Inst Genom Math, Bonn, Germany Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany CHUS, Galician Fdn Genom Med SERGAS, Santiago De Compostela, Spain Aarhus Univ, Dept Biomed, Aarhus, Denmark Aarhus Univ, iSEQ, Ctr Integrat Sequencing, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark Fdn FondaMental, Creteil, France Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland Wellcome Trust Sanger Inst, Cambridge, England South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, Dept Neurosci, London, England Kings Coll London, London, England DFG Res Ctr Mol Physiol Brain CMPB, Gottingen, Germany Max Planck Inst Expt Med, Div Clin Neurosci, D-37075 Gottingen, Germany Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland Univ Iceland, Sch Med, Reykjavik, Iceland Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London, England Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80539 Munich, Germany Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany Univ Aberdeen, Dept Mental Hlth, Royal Cornhill Hosp, Aberdeen, Scotland Ravenscraig Hosp, Greenock, Scotland [Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict,Oslo Univ Hosp, Oslo, Norway Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland Univ Helsinki, Cent Hosp, Helsinki, Finland Natl Inst Hlth & Welf THL, Publ Hlth Genom Unit, Helsinki, Finland Univ Copenhagen, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Roskilde, Denmark Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark Aarhus Univ Hosp, Dept Mol Med, DK-8000 Aarhus, Denmark H Lundbeck & Co AS, Synapt Transmiss, Copenhagen, Denmark Copenhagen Univ Hosp, Psychiat Ctr Copenhagen, Copenhagen, Denmark Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia CHUS, Serv Psychiat, Santiago De Compostela, Spain Univ Valencia, Network Ctr Biomed Res Mental Hlth CIBERSAM, Unit Psychiat, Fac Med, Valencia, Spain Univ Complutense, Hosp Gen Univ Gregorio Maranon, IiSGM, CIBERSAM, E-28040 Madrid, Spain Hop H Mondor A Chenevier, AP HP, Creteil, France Univ Paris Est, Fac Med, Creteil, France Univ Roma Tor Vergata, Dept Neurosci, Sect Psychiat, Rome, Italy Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany Nord Biosci, Herlev, Denmark Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London, England Radboud Univ Nijmegen, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60054 Frankfurt, Germany Univ Trier, Dept Neurobehav Genet, Trier, Germany Natl Univ Hosp Reykjavik, Dept Child & Adolescent Psychiat, Reykjavik, Iceland State Diagnost & Counseling Ctr, Kopavogur, Iceland Ukrainian Res Inst Social Forens Psychiat & Drug, Dept Child Adolescent Psychiat & Med Social Rehab, Kiev, Ukraine Univ Skopje, Dept Child & Adolescent Psychiat, Skopje, Macedonia Inst Mental Hlth, Belgrade, Serbia Univ Belgrade, Fac Med, Belgrade, Serbia Tbilisi State Med Univ TSMU, Dept Psychiat & Drug Addict, Tbilisi, Rep of Georgia Ilia State Univ, Social & Affect Neurosci Lab, Tbilisi, Rep of Georgia Ctr Addict & Mental Hlth CAMH, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada Prince Wales Hosp, Black Dog Inst, Randwick, NSW 2031, Australia Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia Neurosci Res Australia, Sydney, NSW, Australia Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia Queensland Inst Med Res, Brisbane, Qld 4006, Australia Catholic Univ Louvain, Univ Psychiat Ctr, Kortenberg, Belgium Maastricht Univ, European Grad Sch Neurosci EURON,Med Ctr, Sch Mental Hlth & Neurosci,Dept Psychiat & Psycho, South Limburg Mental Hlth Res & Teaching Network, Maastricht, Netherlands Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1085 Budapest, Hungary Karolinska Hosp & Inst, HUBIN Project, Dept Clin Neurosci, Stockholm, Sweden Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands Maastricht Univ, Dept Psychiat, Med Ctr, Maastricht, Netherlands Univ Western Australia, Graylands Hosp, CCRN, Perth, WA 6009, Australia UCL, Mental Hlth Sci Unit, London, England UCL, Inst Cognit Neurosci, London, England South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, Dept Psychosis Studies, London, England Trinity Coll Dublin, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales Univ Santiago de Compostela, Biomed Network Res Ctr Rare Dis CIBERER, Galician Fdn Genom Med, Genom Med Grp, Santiago De Compostela, Spain Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark German Ctr Neurodegenerat Disorders DZNE, Bonn, Germany Univ Bonn, Inst Human Genet, Bonn, Germany Inst Neurosci & Med INM 1, Julich, Germany Univ Verona, Sect Psychiat, I-37100 Verona, Italy Broad Inst MIT & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA Univ Helsinki, Dept Med Genet, Helsinki, Finland Univ Cent Hosp, Helsinki, Finland Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany Eli Lilly & Co Ltd, Erl Wood Manor, Windlesham, Surrey, England, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and RS: MHeNs - R2 - Mental Health

Subjects
Oncology, Male, association, Bipolar disorder, cross-disorder, schizophrenia, 1p11.2, Bipolar Disorder, International Cooperation, Genome-wide association study, Disease, 0302 clinical medicine, Risk Factors, Epidemiology, Odds Ratio, Medicine, genetics [Schizophrenia], Oligonucleotide Array Sequence Analysis, Genetics, Aged, 80 and over, bipolar disorder, 0303 health sciences, Middle Aged, 16p11.2, 3. Good health, Europe, Psychiatry and Mental health, genetics [Chromosomes, Human, Pair 16], epidemiology [Bipolar Disorder], Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], genetics [Polymorphism, Single Nucleotide], Female, Adult, medicine.medical_specialty, Psychosis, Genotype, complications [Bipolar Disorder], epidemiology [Schizophrenia], Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, complications [Schizophrenia], Internal medicine, mental disorders, Humans, Genetic Predisposition to Disease, ddc:610, Molecular Biology, Settore MED/25 - Psichiatria, 030304 developmental biology, Aged, Chromosome Aberrations, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Gene Expression Profiling, Odds ratio, medicine.disease, Schizophrenia, Autism, business, Body mass index, genetics [Bipolar Disorder], 030217 neurology & neurosurgery, Chromosomes, Human, Pair 16, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders). National Institute of Mental Health N01 MH900001 MH074027 1U24MH081810 R01 MH078075 Eli Lilly and Company Pritzker Neuropsychiatric Disorders Research Fund L.L.C. Massachusetts General Hospital in Boston, MA (NIMH) 2N01MH080001-001 Wellcome Trust 076113 085475 075491/Z/04 085475/B/08/Z 085475/Z/08/Z Medical Research Council G0601030 Anthony P Monaco, PI, University of Oxford National Genome Research Network of the German Federal Ministry of Education and Research (BMBF) 01GS08144 01GS08147 Centre of Excellence for Complex Disease Genetics of the Academy of Finland 213506 129680 Biocentrum Helsinki Foundation Research Program for Molecular Medicine, Faculty of Medicine, University of Helsinki Stanley Medical Research Institute Danish Council for Strategic Research 2101-07-0059 H Lundbeck A/S; the Research Council of Norway 163070/V50 Danish Medical Research Council South-East Norway Health Authority 2004-123 Medical Research Council Ministerio de Sanidad y Consumo, Spain PI081522 Xunta de Galicia 08CSA005208PR Swedish Research Council Wellcome Trust Case Control Consortium 2 Max Planck Society; Saarland University T6 03 10 00-45 Netherlands Foundation for Brain Research (Hersenstichting) 2008(1).34 2006-037761 PIAP-GA-2008-218251 HEALTH-F2-2009-223423 HEALTH-F4-2009-242257 info:eu-repo/grantAgreement/EC/FP7/218251

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results