19 results on '"Uhr M"'
Search Results
2. Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization
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Auffenberg, E., Jurik, A., Mattusch, C., Stoffel, R., Genewsky, A., Namendorf, C., Schmid, R., Rammes, G., Biel, M., Uhr, M., Moosmang, S., Michalakis, S., Wotjak, C., and Thoeringer, C.
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Neurons ,Potassium Channels ,Behavior, Animal ,Protein Stability ,Morpholines ,Tacrolimus Binding Protein 1A ,Article ,Cell Line ,Mice ,Memory ,Animals ,Humans ,Protein Interaction Domains and Motifs ,Potassium Channels, Inwardly Rectifying - Abstract
Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms. The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research.
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- 2016
3. The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1
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Castillo-Gomez, E., Kästner, A., Steiner, J., Schneider, A., Hettling, B., Poggi, G., Ostehr, K., Uhr, M., Asif, A., Matzke, M., Schmidt, U., Pfander, V., Hammer, C., Schulz, T., Binder, L., Stöcker, W., Weber, F., and Ehrenreich, H.
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Adult ,Male ,Multiple Sclerosis ,Brain ,Middle Aged ,Receptors, N-Methyl-D-Aspartate ,blood [Multiple Sclerosis] ,Mice, Inbred C57BL ,Mice ,cerebrospinal fluid [Autoantibodies] ,Blood-Brain Barrier ,immunology [Receptors, N-Methyl-D-Aspartate] ,Seroepidemiologic Studies ,Animals ,Humans ,blood [Autoantibodies] ,immunology [Brain] ,Female ,ddc:610 ,NR1 NMDA receptor ,physiopathology [Blood-Brain Barrier] ,cerebrospinal fluid [Multiple Sclerosis] ,Autoantibodies - Abstract
Autoantibodies (AB) against N-methyl-D-aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood-brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF-serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non-brain-binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an 'immunoprecipitator'; simultaneous injection of NMDAR1 AB and the non-brain-binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF.
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- 2016
4. The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects: Results in ~25,000 subjects
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Peyrot, W. J., Lee, S. H., Milaneschi, Y., Abdellaoui, A., Byrne, E. M., Esko, T., de Geus, E. J. C., Hemani, G., Hottenga, J. J., Kloiber, S., Levinson, D. F., Lucae, S., Martin, N. G., Medland, S. E., Metspalu, A., Milani, L., Noethen, M. M., Potash, J. B., Rietschel, M., Rietveld, C. A., Ripke, S., Shi, J., Willemsen, G., Zhu, Z., Boomsma, D. I., Wray, N. R., Penninx, B. W. J. H., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., Blackwood, D. H., Cichon, S., Heath, A. C., Holsboer, F., Madden, Pamela A., McGuffin, P., Muglia, P., Pergadia, M. L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H. J., Lichtenstein, P., Magnusson, P., Perlis, R. H., Preisig, M., Smoller, J. W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K. E., Teumer, A., Viktorin, A., Barnes, M. R., Bettecken, T., Binder, E. B., Breuer, R., Castro, V. M., Churchill, S. E., Coryell, W. H., Craddock, N., Craig, I. W., Czamara, D., Degenhardt, F., Farmer, A. E., Fava, M., Frank, J., Gainer, V. S., Gallagher, P. J., Gordon, S. D., Goryachev, S., Gross, M., Guipponi, M., Henders, A. K., Herms, S., Hickie, I. B., Hoefels, S., Hoogendijk, W., Iosifescu, D. V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J. A., Kohane, I. S., Kohli, M. A., Korszun, A., Landen, M., Lawson, W. B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P. J., McIntosh, A., McLean, A., Middeldorp, C. M., Middleton, L., Montgomery, G. M., Murphy, S. N., Nauck, M., Nolen, W. A., Nyholt, Dale R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W. A., Schulz, A., Schulze, T. G., Shyn, S. I., Sigurdsson, E., Slager, S. L., Smit, J. H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E. J., van Grootheest, G., Völzke, H., Weilburg, J. B., Zitman, F. G., Neale, B., Daly, M., Sullivan, P. F., Agrawal, Arpana, Albrecht, Eva, Z Alizadeh, Behrooz, Allik, J. ri, Amin, Najaf, Attia, John R., Bandinelli, Stefania, Barnard, John, Bastardot, Franois, e Baumeister, Sebastian, Beauchamp, Jonathan, Benjamin, Daniel J., Benke, Kelly S., Bennett, David A., Berger, Klaus, Bielak, Lawrence F., Bierut, Laura J., Boatman, Jeffrey A., Boyle, Patricia A., Bültmann, Ute, Campbell, Harry, Cesarini, David, Chabris, Christopher F., Cherkas, Lynn, Chung, Mina K., Conley, Dalton, Cucca, Francesco, Davey-Smith, George, Davies, Gail, de Andrade, Mariza, de Jager, Philip L., de Leeuw, Christiaan, de Neve, Jan-Emmanuel, Deary, Ian J., Dedoussis, George V., Deloukas, Panos, Derringer, Jaime, Dimitriou, Maria, Eiriksdottir, Gudny, Eklund, Niina, Elderson, Martin F., Eriksson, Johan G., Evans, Daniel S., Evans, David M., Faul, Jessica D., Fehrmann, Rudolf, Ferrucci, Luigi, Fischer, Krista, Franke, Lude, Garcia, Melissa E., Gieger, Christian, Gjessing, Hkon K., Groenen, Patrick J. F., Grönberg, Henrik, Gudnason, Vilmundur, Hägg, Sara, Hall, Per, Harris, Jennifer R., Harris, Juliette M., Harris, Tamara B., Hastie, Nicholas D., Hayward, Caroline, Hernandez, Dena G., Hoffmann, Wolgang, Hofman, Adriaan, Hofman, Albert, Holle, Rolf, Holliday, Elizabeth G., Holzapfel, Christina, Iacono, William G., Ibrahim-Verbaas, Carla A., Illig, Thomas, Ingelsson, Erik, Jacobsson, Bo, Järvelin, Marjo-Riitta, Jhun, Min A., Johannesson, Magnus, Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika, Kähönen, Mika, Kanoni, Stavroula, Kaprio, Jaakkko, Kardia, Sharon L. R., Karjalainen, Juha, Kirkpatrick, Robert M., Koellinger, Philipp D., Kolcic, Ivana, Kowgier, Matthew, Kristiansson, Kati, Krueger, Robert F., Kutalik, Z. ltan, Lahti, Jari, Laibson, David, Latvala, Antti, Launer, Lenore J., Lawlor, Debbie A., Lethimäki, Terho, Li, Jingmei, Lichtenstein, Paul, Lichtner, Peter K., Liewald, David C., Lin, Peng, Lind, Penelope A., Liu, Yongmei, Lohman, Kurt, Loitfelder, Marisa, Magnusson, Patrick K. E., Mäkinen, Tomi E., Vidal, Pedro Marques, Martin, Nicolas W., Masala, Marco, McGue, Matt, McMahon, George, Meirelles, Osorio, Meyer, Michelle N., Mielck, Andreas, Miller, Michael B., Montgomery, Grant W., Mukherjee, Sutapa, Myhre, Ronny, Nuotio, Marja-Liisa, J Oldmeadow, Christopher, Oostra, Ben A., Palmer, Lyle J., Palotie, Aarno, Perola, Markus, Petrovic, Katja E., Peyser, Patricia A., Polašek, Ozren, Posthuma, Danielle, Preisig, Martin, Quaye, Lydia, Räikkönen, Katri, Raitakari, Olli T., Realo, Anu, Reinmaa, Eva, Rice, John P., Ring, Susan M., Ripatti, Samuli, Rivadeneira, Fernando, Rizzi, Thais S., Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sarin, Antti-Pekka, Schlessinger, David, Schmidt, Helena, Schmidt, Reinhold, Scott, Rodney J., Shakhbazov, Konstantin, Smith, Albert V., Smith, Jennifer A., Snieder, Harold, St Pourcain, Beate, Starr, John M., Sul, Jae Hoon, Surakka, Ida, Svento, Rauli, Tanaka, Toshiko, Terracciano, Antonio, Teumer, Alexander, Thurik, A. Roy, Tiemeier, Henning, Timpson, Nicholas J., Uitterlinden, André G., van der Loos, Matthijs J. H. M., van Duijn, Cornelia M., van Rooij, Frank J. A., van Wagoner, David R., Vartiainen, Erkki, Viikari, Jorma, Visscher, Peter M., Vitart, Veronique, Vollenweider, Peter K., Völzke, Henry, Vonk, Judith M., Waeber, G. rard, Weir, David R., Wellmann, J. rgen, Westra, Harm-Jan, Wichmann, H. Erich, Widen, Elisabeth, Wilson, James F., Wright, Alan F., Yang, Jian, Yu, Lei, Zhao, Wei, and Academic Medical Center
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Adult ,Male ,Psychiatric Status Rating Scales ,Likelihood Functions ,Genotype ,Estonia/epidemiology ,Netherlands/epidemiology ,Depressive Disorder, Major/epidemiology ,Middle Aged ,Polymorphism, Single Nucleotide/genetics ,Cohort Studies ,Odds Ratio ,Educational Status ,Humans ,Regression Analysis ,Female ,Gene-Environment Interaction ,Genetic Association Studies ,Aged - Abstract
An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.
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- 2015
5. Association of FKBP51 with Priming of Autophagy Pathways and Mediation of Antidepressant Treatment Response: Evidence in Cells, Mice, and Humans
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Gassen, N., Hartmann, J., Zschocke, J., Stepan, J., Hafner, K., Zellner, A., Kirmeier, T., Kollmannsberger, L., Wagner, K., Dedic, N., Balsevich, G., Deussing, J., Kloiber, S., Lucae, S., Holsboer, F., Eder, M., Uhr, M., Ising, M., Schmidt, M., and Rein, T.
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Adult ,Male ,Psychopharmacology ,Amitriptyline ,lcsh:Medicine ,Biochemistry ,Rats, Sprague-Dawley ,Tacrolimus Binding Proteins ,Behavioral Neuroscience ,Young Adult ,Molecular Cell Biology ,Mental Health and Psychiatry ,Medicine and Health Sciences ,Autophagy ,Animals ,Humans ,Molecular Biology ,Pharmacology ,Mice, Knockout ,Depressive Disorder ,Blood Cells ,Depression ,lcsh:R ,Biology and Life Sciences ,Membrane Proteins ,Cell Biology ,Middle Aged ,Antidepressive Agents ,Mice, Inbred C57BL ,Paroxetine ,Leukocytes, Mononuclear ,Beclin-1 ,Female ,Apoptosis Regulatory Proteins ,Biomarkers ,Stress, Psychological ,Research Article ,Neuroscience - Abstract
Theo Rein and colleagues examine the role of FKBP51 in the actions of antidepressants, with a particular focus on pathways of autophagy. Please see later in the article for the Editors' Summary, Background FK506 binding protein 51 (FKBP51) is an Hsp90 co-chaperone and regulator of the glucocorticoid receptor, and consequently of stress physiology. Clinical studies suggest a genetic link between FKBP51 and antidepressant response in mood disorders; however, the underlying mechanisms remain elusive. The objective of this study was to elucidate the role of FKBP51 in the actions of antidepressants, with a particular focus on pathways of autophagy. Methods and Findings Established cell lines, primary neural cells, human blood cells of healthy individuals and patients with depression, and mice were treated with antidepressants. Mice were tested for several neuroendocrine and behavioral parameters. Protein interactions and autophagic pathway activity were mainly evaluated by co-immunoprecipitation and Western blots. We first show that the effects of acute antidepressant treatment on behavior are abolished in FKBP51 knockout (51KO) mice. Autophagic markers, such as the autophagy initiator Beclin1, were increased following acute antidepressant treatment in brains from wild-type, but not 51KO, animals. FKBP51 binds to Beclin1, changes decisive protein interactions and phosphorylation of Beclin1, and triggers autophagic pathways. Antidepressants and FKBP51 exhibited synergistic effects on these pathways. Using chronic social defeat as a depression-relevant stress model in combination with chronic paroxetine (PAR) treatment revealed that the stress response, as well as the effects of antidepressants on behavior and autophagic markers, depends on FKBP51. In human blood cells of healthy individuals, FKBP51 levels correlated with the potential of antidepressants to induce autophagic pathways. Importantly, the clinical antidepressant response of patients with depression (n = 51) could be predicted by the antidepressant response of autophagic markers in patient-derived peripheral blood lymphocytes cultivated and treated ex vivo (Beclin1/amitriptyline: r = 0.572, p = 0.003; Beclin1/PAR: r = 0.569, p = 0.004; Beclin1/fluoxetine: r = 0.454, p = 0.026; pAkt/amitriptyline: r = −0.416, p = 0.006; pAkt/PAR: r = −0.355, p = 0.021; LC3B-II/PAR: r = 0.453, p = 0.02), as well as by the lymphocytic expression levels of FKBP51 (r = 0.631, p, Editors' Summary Background Everyone feels miserable sometimes, but about one in six people will have an episode of clinical depression during their lifetime. For people who are clinically depressed, overwhelming feelings of sadness, anxiety, and hopelessness can last for months or years. Affected individuals lose interest in activities they used to enjoy, they sometimes have physical symptoms such as disturbed sleep, and they may contemplate suicide. Clinicians diagnose depression and determine its severity using questionnaires (“depression rating scales”) that explore the patient's feelings and symptoms. Mild depression is often treated with talking therapies (psychotherapy) such as cognitive behavioral therapy, which helps people change negative ways of thinking. For more severe depression, patients are also usually prescribed an antidepressant, most commonly a “selective serotonin reuptake inhibitor” such as paroxetine or a tricyclic antidepressant such as amitriptyline. Why Was This Study Done? Unfortunately, antidepressants don't work for more than half of patients. Moreover, because it is unclear how antidepressants work, it is not possible to predict which patients will respond to which antidepressants. Thus, matching patient to drug can be a lengthy, sometimes unsuccessful, process. Here, the researchers use several approaches to test the hypothesis that a protein called FK506 binding protein 51 (FKBP51) is involved in the actions of antidepressants and to investigate whether the ability of both FKBP51 and antidepressants to regulate a process called autophagy underlies the impact of FKBP51 on antidepressant responses. FKBP51 is a regulator of stress physiology, which is connected to the development and treatment of depression; genetic studies have suggested a link between FKBP51 expression and the antidepressant response rate. Some antidepressants are known to alter the initial steps in the autophagy pathway, a multistep process that maintains the integrity of cells through regulated degradation and recycling of cellular components; however, the potential synergistic role of FKBP51 and antidepressants in regulating pathways of autophagy are unknown. What Did the Researchers Do and Find? The researchers first treated wild-type mice and FKBP51 knockout mice (genetically altered animals that make no FKBP51) with an acute dose of antidepressant and compared their behavior in a forced swim test, an assay that measures the action of antidepressants in mice by determining how long the mice struggle or float inertly when placed in deep water. As expected, acute antidepressant treatment increased the time that wild-type mice spent struggling. However, this effect of antidepressant treatment was greatly attenuated in the FKBP51 knockout mice. Moreover, the levels of several autophagy markers increased in the brains of wild-type mice following antidepressant treatment but not in the brains of FKBP51 knockout mice. Next, using “chronic social defeat stress” to model the “endophenotype” of depression (a combination of physiological, hormonal, and behavioral traits seen in people with depression) in mice, the researchers showed that the stress response and the effect of chronic antidepressants on behavior and on autophagic markers all depend on FKBP51. Using cell-based assays, the researchers showed that antidepressants and FKBP51 had synergistic (interactive) effects on the autophagic pathway and that, in human blood cells, FKBP51 levels correlated with the potential of antidepressants to induce autophagic pathways. Finally, the researchers report that the clinical response to antidepressant treatment in 51 patients with depression was associated with the response of autophagic markers in their peripheral blood lymphocytes to antidepressant treatment in test tubes, and that the expression levels of FKBP51 and autophagy markers in patient lymphocytes at admission were associated with subsequent clinical responses to antidepressants. What Do These Findings Mean? These findings suggest that the protein FKBP51 is required for the effects of both acute and chronic treatment with some antidepressants on behavior and on autophagic pathways in mice. These findings also reveal an association between antidepressant treatment responses in patients and both the expression levels of FKBP51 and autophagy markers in lymphocytes at admission and the response of autophagic markers to antidepressant treatment in patient lymphocytes. The accuracy of these findings is limited by the small number of clinical samples available for analysis, by the use of only male mice in the animal experiments, and by the inability of animal models of depression to fully replicate the human condition. Nevertheless, these findings identify the early stages of autophagy as potential targets for the development of new antidepressants and identify several potential biomarkers that might, after further clinical validation, help clinicians predict antidepressant efficacy in patients with depression. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001755. The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish), including information on antidepressants The UK National Health Service Choices website provides detailed information about depression and about antidepressants; it also provides personal stories about depression The UK charity Mind provides information on depression, including some personal stories about depression More personal stories about depression are available from healthtalk.org MedlinePlus provides links to other resources about depression Wikipedia has a page on autophagy (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) The patients included in this study were all enrolled in the Munich Antidepressant Response Signature project, which aims to identify gene variants and biomarkers that predict treatment outcomes with antidepressants
- Published
- 2014
6. Identification of risk loci with shared effects on five major psychiatric disorders:a genome-wide analysis
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Smoller, J.W., Ripke, S., Lee, P.H., Neale, B., Nurnberger, J.I., Santangelo, S., Sullivan, P.F., Perlis, R.H., Purcell, S.M., Fanous, A., Neale, M.C., Rietschel, M., Schulze, T.G., Thapar, A., Anney, R., Buitelaar, J.K., Farone, S.V., Hoogendijk, W.J.G., Levinson, D.F., Lesch, K.P., Riley, B., Schachar, R., Sonuga-Barke, E.J., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Arking, D., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Banaschewski, T., Barchas, J.D., Barnes, M.R., Bass, N., Bauer, M.C.R., Bellivier, F., Bergen, S.E., Berrettini, W., Bettecken, T., Biederman, J, Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breen, G., Breuer, R., Buccola, N.G., Bunner, W.E., Burmeister, M., Buxbaum, J.D., Byerley, W. F., Sian, C., Cantor, R.M., Chakravarti, A., Chambert, K., Chicon, S., Cloniger, C.R., Collier, D.A., Cook, E., Coon, H., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I.W., Curtis, D., Czamara, D., Daly, M., Datta, S., Day, R., de Geus, E.J.C., Degenhardt, F., Devlin, B., Srdjan, D., Doyle, A.E., Duan, J., Dudbridge, F., Edenberg, H.J., Elkin, A., Etain, B., Farmer, A.E., Ferreira, M.A.R., Ferrier, I.N., Flickinger, M., Foroud, T., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Friedl, M., Frisén, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S.D., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Gross, M., Grozeva, D., Guan, W., Gurling, H., Gustafsson, O., Hakonarson, H., Hamilton, S.P., Hamshere, M.L., Hansen, T.F., Hartmann, A.M., Hautzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I.B., Hipolito, M., Hoefels, S., Holmans, P.A., Holsboer, F., Hottenga, J.J., Hultman, C. M., Ingason, A., Ising, M., Jamain, S., Jones, E.G., Jones, L., Jones, I., Jung-Ying, T., Kahler, A., Kandaswamy, R., Keller, M.C., Kelsoe, J., Kennedy, J.L., Kenny, E., Kim, Y., Kirov, G. K., Knowles, J.A., Kohli, M.A., Koller, D.L., Konte, B., Korszun, A., Krasucki, R., Kuntsi, J., Phoenix, K., Landén, M., Langstrom, N., Lathrop, M., Lawrence, J., Lawson, W.B., Leboyer, M., Lencz, T., Lewis, C.M., Li, J., Lichtenstein, P., Lieberman, J. A., Lin, D., Liu, C., Lohoff, F.W., Loo, S.K., Lucae, S., MacIntyre, D.J., Madden, P.A.F., Magnusson, P., Mahon, P.B., Maier, W., Malhotra, A.K., Mattheisen, M., Matthews, K., Mattingsdal, M., McCarroll, S., McGhee, K.A., McGough, J.J., McGrath, P.J., McGuffin, P., McInnis, M.G., McIntosh, A., McKinney, R., McClean, A.W., McMahon, F.J., McQuillin, A., Medeiros, H., Medland, S.E., Meier, S., Melle, I., Meng, F., Middeldorp, C.M., Middleton, L., Vihra, M., Mitchell, P.B., Montgomery, G.W., Moran, J., Morken, G., Morris, D.W., Moskvina, V., Mowry, B. J., Muglia, P., Mühleisen, T.W., Muir, W.J., Müller-Myhsok, B., Myers, R.M., Nelson, S.F., Nievergelt, C.M., Nikolovq, I., Nimgaonkar, V.L., Nolen, W.A., Nöthen, M.M., Nwulia, E.A., Nyholt, DR, O'Donovan, M.C., O'Dushlaine, C., Oades, R.D., Olincy, A., Olsen, L., Ophoff, R.A., Osby, U., Óskarsson, H., Owen, M.J., Palotie, A., Pato, M.T., Pato, C.N., Penninx, B.W.J.H., Pergadia, M.L., Petursson, H., Pickard, B.S., Pimm, J., Piven, J., Porgeirsson, P., Posthuma, D., Potash, J.B., Propping, J., Puri, V., Quested, D., Quinn, E.M., Rasmussen, H.B., Raychaudhuri, S., Rehnström, K., Reif, A., Rice, J., Rossin, L., Rothenberger, A., Rouleau, G., Ruderfer, D., Rujescu, D., Sanders, A.R., Schalling, M., Schatzberg, A.F., Scheftner, W.A., Schellenberg, G.D., Schofield, P.R., Schork, N.J., Schumacher, J., Schwarz, M.M., Scolnick, E., Scott, L.J., Shi, J., Shillling, P.D., Shyn, S.I., Sigurdsson, E., Silverman, J.M., Sklar, P., Slager, S.L., Smalley, S.L., Smit, J.H., Smith, E.N., Sonuga-Barke, E., St Clair, D., State, M., Stefansson, K., Stefansson, H., Steffans, M., Steinberg, S., Steinhausen, H.C., Strauss, J., Strohmaier, J., Stroup, T.S., Sutcliffe, J., Szatmari, P., Szelinger, S., Thirumalai, S., Thompson, R.C., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Grootheest, G., Vieland, V., Vincent, J.B., Visscher, P.M., Watson, S.J., Weissman, M.M., Werge, T., Wienker, T.F., Willemsen, G., Williamson, R., Witt, S.H., Wray, N.R., Wright, A., Xu, W., Young, A.H., Zammit, S., Zandi, P.P., Zhang, P., Zitman, F.G., Zöllner, S., Kendler, K.S., Psychiatry, Human genetics, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Oades, Robert D. (Beitragende*r), and Oades, Robert D.
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Netherlands Twin Register (NTR) ,Adult ,medicine.medical_specialty ,Bipolar Disorder ,Calcium Channels, L-Type ,Population ,Medizin ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Article ,Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3] ,medicine ,ddc:61 ,Attention deficit hyperactivity disorder ,Humans ,DCN PAC - Perception action and control NCEBP 9 - Mental health ,ddc:610 ,Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters ,Bipolar disorder ,Age of Onset ,Psychiatry ,education ,Child ,Genetics ,education.field_of_study ,Depressive Disorder, Major ,General Medicine ,Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3] ,medicine.disease ,Logistic Models ,Autism spectrum disorder ,Schizophrenia ,Attention Deficit Disorder with Hyperactivity ,Child Development Disorders, Pervasive ,Genetic Loci ,Expression quantitative trait loci ,Major depressive disorder ,Genome-Wide Association Study - Abstract
Item does not contain fulltext BACKGROUND: Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. METHODS: We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. FINDINGS: SNPs at four loci surpassed the cutoff for genome-wide significance (p
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- 2013
7. A mega-analysis of genome-wide association studies for major depressive disorder
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Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, Breen G, Byrne EM, Blackwood DH, Boomsma DI, Cichon S, Heath AC, Holsboer F, Lucae S, Madden PA, Martin NG, Penninx BP, De Geus EJ, Hottenga JJ, Middeldorp CM, Steffens M, Thorgeirsson T, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Vxf6lzke H, Weilburg JB, Willemsen G, Zitman FG, Neale B, Daly M, Levinson DF, and Sullivan PF
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- 2013
8. A mega-analysis of genome-wide association studies for major depressive disorder
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Ripke, S, Wray, NR, Lewis, CM, Hamilton, SP, Weissman, MM, Breen, G, Byrne, EM, Blackwood, DHR, Boomsma, DI, Cichon, S, Heath, AC, Holsboer, F, Lucae, S, Madden, PA, Martin, NG, McGuffin, P, Muglia, P, Noethen, MM, Penninx, BP, Pergadia, ML, Potash, JB, Rietschel, M, Lin, DY, Muller-Myhsok, B, Shi, J, Steinberg, S, Grabe, HJ, Lichtenstein, P, Magnusson, P, Perlis, RH, Preisig, M, Smoller, JW, Stefansson, K, Uher, R, Kutalik, Z, Tansey, KE, Teumer, A, Viktorin, A, Barnes, MR, Bettecken, T, Binder, EB, Breuer, R, Castro, VM, Churchill, SE, Coryell, WH, Craddock, N, Craig, IW, Czamara, D, de Geus, EJC, Degenhardt, F, Farmer, AE, Fava, M, Frank, J, Gainer, VS, Gallagher, PJ, Gordon, SD, Goryachev, S, Gross, M, Guipponi, M, Henders, AK, Herms, S, Hickie, IB, Hoefels, S, Hoogendijk, Witte, Hottenga, JJ (Jouke Jan), Iosifescu, DV, Ising, M, Jones, I, Jones, L, Jung-Ying, T, Knowles, JA, Kohane, IS, Kohli, MA, Korszun, A, Landen, M, Lawson, WB, Lewis, G, MacIntyre, DJ, Maier, W, Mattheisen, M, McGrath, PJ, McIntosh, A, McLean, AW, Middeldorp, CM (Christel), Middleton, L, Montgomery, GM, Murphy, SN, Nauck, M, Nolen, WA, Nyholt, DR, O' Donovan, M, Oskarsson, H, Pedersen, N, Scheftner, WA, Schulz, TG, Shyn, SI, Sigurdsson, E, Slager, SL, Smit, JH, Stefansson, H, Steffens, M, Thorgeirsson, T, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, EJCG (Edwin), Van Grootheest, G, Volzke, H, Weilburg, JB, Willemsen, G, Zitman, FG, Neale, BM, Daly, M, Levinson, DF, Sullivan, PF, Psychiatry, Epidemiology, and Child and Adolescent Psychiatry / Psychology
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- 2013
9. More CLEC16A gene variants associated with multiple sclerosis
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Nischwitz, S., Cepok, S., Kroner, A., Wolf, C., Knop, M., Müller-Sarnowski, Felix, Pfister, H., Rieckmann, P., Hemmer, B., Ising, M., Uhr, M., Bettecken, T., Holsboer, F., Müller-Myhsok, B., and Weber, F.
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- 2010
10. Mechanisms underlying the protective potential of alpha-tocopherol (vitamin E) against haloperidol-associated neurotoxicity
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Post, A., Rucker, M., Ohl, F., Uhr, M., Holsboer, F., Almeida, O. F. X., and Michaelidis, T. M.
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p53 ,tumor-suppressor p53 ,nervo ,apoptosis ,neuroleptic drug haloperidol ,nf-kappa b/i kappa-b ,tardive-dyskinesia ,haloperidol ,elevated plus-maze ,tardive dyskinesia ,bax ,nf-kappa-b ,oxidative stress ,vacuous chewing movements ,programmed cell-death - Abstract
The undesired side-effects of haloperidol treatment include a number of extrapyramidal side-effects which have been proposed to result from drug-induced damage to the basal ganglia. The drug also causes irregular movements and locomotor patterns in experimental animals. Here we show that haloperidol treatment in rats is associated with increases in the expression of 1753 and the ratio of pro-apoptotic (Bax) to anti-apoptotic (Bcl-2/Bcl-x(1)) proteins in the hippocampus and caudate putamen (CPu). In addition, haloperidol induces the DNA binding activity of the redox-sensitive nuclear factor-kappa B (NF-kappaB) and concomitantly upregulates the levels of the phosphorylated form of IkappaBalpha protein in vivo. Similar responses are observed when a mouse hippocampal cell line (HT-22) is treated with haloperidol and/or vitamin E. Interestingly, all of these biochemical effects of haloperidol arc significantly attenuated when animals or cultured cells are pretreated with a-tocopherol (vitamin E). Consistent with this, vitamin E is demonstrated to substantially reduce the haloperidol-induced impairment of locomotor activity in rats. Collectively, the data indicate the usefulness of vitamin E as an adjunct to haloperidol treatment and provide initial clues about the underlying molecular mechanisms involved in these effects. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. Neuropsychopharmacology
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- 2002
11. Causal therapy of Parkinson's disease with anle138b, a novel protein aggregation inhibitor
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Johannes Levin, Wagner, J., Ryazanov, S., Leonov, A., Shi, S., Schmidt, F., Prix, C., Bertsch, U., Mitteregger-Kretzschmar, G., Geissen, M., Hirschberger, T., Tavan, P., Pilger, J., Zweckstetter, M., Frank, T., Baehr, M., Weishaupt, J., Uhr, M., Urlaub, H., Teichmann, U., Boetzel, K., Groschup, M., Kretzschmar, H. A., Griesinger, C., and Giese, A.
12. c-kit protein (stem cell factor receptor) expression on cells with erythroid characteristics and on normal human bone marrow without the use of monoclonal antibodies
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Colin McGuckin, Uhr, M. R., and Gordon-Smith, Edward C.
13. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011,Linee guida della consensus conference dell'ANGP per il monitoraggio plasmatico dei farmaci (TDM) in psichiatria. Aggiornamento 2011
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Hiemke, C., Baumann, P., Bergemann, N., Dietmaier, O., Karin Maria Egberts, Fric, M., Gerlach, M., Greiner, C., Gründer, G., Haen, E., Havemann-Reinecke, U., Jaquenoud Sirot, E., Kirchherr, H., Laux, G., Lutz, U. C., Messer, T., Müller, M. J., Pfuhlmann, B., Rambeck, B., Riederer, P., Schoppek, B., Stingl, J., Uhr, M., Ulrich, S., Waschgler, R., Zernig, G., Conca, A., Broich, K., Deckert, J., Dobmeier, M., Eckermann, G., Jürgens, U., Mehler-Wex, C., Riedel, M., and Schwarz, M.
14. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011,AGNP-konsensus-leitlinien für therapeutisches drug-monitoring in der psychiatrie: Update 2011
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Hiemke, C., Baumann, P., Bergemann, N., Arolsen, B., Conca, A., Dietmaier, O., Karin Maria Egberts, Fric, M., Gerlach, M., Greiner, C., Gründer, G., Haen, E., Havemann-Reinecke, U., Sirot, E. J., Kirchherr, H., Laux, G., Lutz, U. C., Messer, T., Müller, M. J., Pfuhlmann, B., Rambeck, B., Riederer, P., Schoppek, B., Schwarz, M. J., Stingl, J., Uhr, M., Ulrich, S., Waschgier, R., and Zernig, G.
15. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects
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Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Nicholas D. Hastie, Beate St Pourcain, Marcus Ising, Gérard Waeber, Behrooz Z. Alizadeh, Judith M. Vonk, Lawrence F. Bielak, Sang Hong Lee, Wouter J. Peyrot, Thomas Illig, M. M. Weissman, Nicholas J. Timpson, George Dedoussis, Nicholas G. Martin, Tomi E. Mäkinen, Jorma Viikari, Lili Milani, Harold Snieder, Laura J. Bierut, A. C. Heath, Reinhold E. Schmidt, Mariza de Andrade, Vilmundur Gudnason, K. Petrovic, Robert M. Kirkpatrick, Marcela González Gross, William G. Iacono, Michelle N. Meyer, Henry Völzke, Marisa Loitfelder, Maria Dimitriou, Lude Franke, Robert F. Krueger, E. J. C. G. van den Oord, Sven Cichon, Michael Conlon O'Donovan, Ian W. Craig, Shawn N. Murphy, Danielle Posthuma, Brenda W.J.H. Penninx, Aarno Palotie, Roy Thurik, Panos Deloukas, Matt McGue, M. Preisig, Patricia A. Boyle, Osorio Meirelles, Ben A. Oostra, Klaus Berger, G. M. Montgomery, Sharon L.R. Kardia, Peter K. Joshi, K. Stefansson, Paul Lichtenstein, Andrew Heath, Andrea Schulz, Dena G. Hernandez, Debbie A Lawlor, S. P. Hamilton, James B. Potash, Z. Kutalik, Elisabeth Widen, Emil L. Sigurdsson, Rudolf S N Fehrmann, Matthias Nauck, Mikael Landén, Kurt Lohman, S.D. Gordon, Lefkos T. Middleton, Caroline Hayward, Anjali K. Henders, Philipp Koellinger, Jeffrey A. Boatman, G van Grootheest, M. Daly, Jian Yang, Peter Vollenweider, Penelope A. Lind, Stacy Steinberg, Frank J. A. van Rooij, Florian Holsboer, Hkon K. Gjessing, Erkki Vartiainen, Magnus Johannesson, Jingmei Li, David Laibson, Henrik Grönberg, Tõnu Esko, Ivana Kolcic, Niina Eklund, Kelly S. Benke, Henning Tiemeier, Isaac S. Kohane, Nicolas W. Martin, Ronny Myhre, Frans G. Zitman, Arpana Agrawal, James F. Wilson, Michael R. Barnes, Lei Yu, Thorgeir E. Thorgeirsson, Franois Bastardot, Katri Räikkönen, William Lawson, Willem A. Nolen, M. Rietschel, René Breuer, Bertram Müller-Myhsok, James A. Knowles, Grant W. Montgomery, Eva Reinmaa, Rudolf Uher, Andreas Mielck, Luigi Ferrucci, S. E. Medland, Yuri Milaneschi, Philip L. De Jager, Manfred Uhr, A. E. Farmer, Cornelia M. van Duijn, Samuli Ripatti, Marja-Liisa Nuotio, Manuel Mattheisen, Sebastian E. Baumeister, David R. Van Wagoner, Martin Preisig, Fernando Rivadeneira, Peter Lichtner, Christopher Oldmeadow, Hreinn Stefansson, Ian B. Hickie, Darina Czamara, Elizabeth G. Holliday, Astanand Jugessur, Carla A. Ibrahim-Verbaas, Jaime Derringer, Vivian S. Gainer, P. Muglia, Daniel J. Benjamin, Patrick K.E. Magnusson, Patience J. Gallagher, Jennifer A. Smith, Lynn Cherkas, Pamela A. F. Madden, David A. Bennett, Zoltán Kutalik, George Davey-Smith, Gudny Eiriksdottir, Jens Treutlein, N. Craddock, Juliette Harris, Antti Latvala, Roy H. Perlis, Markus M. Noethen, Jan-Emmanuel De Neve, Stanley I. Shyn, J.H. Smit, Dalton Conley, Adriaan Hofman, Jari Lahti, Patrick J. F. Groenen, Jüri Allik, Albert V. Smith, Ozren Polasek, Susan M. Ring, Thomas Bettecken, Michele L. Pergadia, Patrick J. McGrath, Katherine E. Tansey, Stephan Ripke, Hogni Oskarsson, Peng Lin, Douglas F. Levinson, Matthijs J. H. M. van der Loos, Melissa E. Garcia, Jonathan P. Beauchamp, Rodney J. Scott, Zhihong Zhu, Michel Guipponi, Lyle J. Palmer, Alexander Teumer, William Coryell, Stefan Kloiber, Gonneke Willemsen, John Frank, Victor M. Castro, Andrew M. McIntosh, John M. Starr, Antonio Terracciano, Mika Kähönen, Marco Masala, Markus Perola, André G. Uitterlinden, Sutapa Mukherjee, Alexander Viktorin, Lenore J. Launer, Elisabeth B. Binder, William A. Scheftner, Christel M. Middeldorp, D. H. R. Blackwood, I. Jones, Thais S. Rizzi, A. Teumer, Cornelius A. Rietveld, Aldo Rustichini, Guy Lewis, Susan L. Slager, David M. Evans, Dorret I. Boomsma, Harry Campbell, Susanne Churchill, Johan G. Eriksson, Alan F. Wright, Dan V. Iosifescu, W. Maier, Francesco Cucca, Federica Tozzi, David R. Weir, Eva Albrecht, L. Milani, Jennifer R. Harris, Min A. Jhun, Marjo-Riitta Järvelin, Martin F. Elderson, Ute Bültmann, Olli T. Raitakari, Konstantin Shakhbazov, Krista Fischer, Thomas G. Schulze, T. Jung-Ying, P. Lichtenstein, Terho Lethimäki, Jeffrey B. Weilburg, Rolf Holle, Bo Jacobsson, Pedro Marques Vidal, Jordan W. Smoller, Stavroula Kanoni, Kati Kristiansson, Sergey Goryachev, Michael Steffens, Peter M. Visscher, Toshiko Tanaka, Donald J. MacIntyre, Witte J.G. Hoogendijk, David Schlessinger, Ian J. Deary, Harm-Jan Westra, Erik Ingelsson, E.J.C. de Geus, Franziska Degenhardt, Lydia Quaye, John Barnard, David C. Liewald, John P. Rice, Christopher F. Chabris, P. McGuffin, Tamara B. Harris, C. M. Lewis, Gail Davies, Enda M. Byrne, H.-Erich Wichmann, Sara Hägg, David Cesarini, Najaf Amin, Juha Karjalainen, Dale R. Nyholt, Christian Gieger, Per Hall, Ania Korszun, Neale Bm, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Jae Hoon Sul, Christiaan de Leeuw, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Mina K. Chung, N. L. Pedersen, Gerome Breen, P. A. F. Madden, Martin A. Kohli, J Kaprio, John Attia, Jing Shi, Gibran Hemani, Rauli Svento, Veronique Vitart, Susanne Lucae, L. A. Jones, Jouke-Jan Hottenga, Daniel S. Evans, Hans-Jörgen Grabe, Yongmei Liu, Danyu Lin, Albert Hofman, George McMahon, Naomi R. Wray, Stefan Herms, Stefania Bandinelli, W. Hoffmann, P.F. Sullivan, Susanne Hoefels, Michael B. Miller, Alan W. McLean, Igor Rudan, Jürgen Wellmann, Anu Realo, Maurizio Fava, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Faculteit Medische Wetenschappen/UMCG, Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Social Science Genetic Association Consortium, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Applied Economics, Biological Psychology, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator, Lewis, C.M., Hamilton, S.P., Weissman, M.M., Breen, G., Blackwood, D.H., Cichon, S., Heath, A.C., Holsboer, F., Madden, P.A., McGuffin, P., Muglia, P., Pergadia, M.L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H.J., Lichtenstein, P., Magnusson, P., Perlis, R.H., Preisig, M., Smoller, J.W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K.E., Teumer, A., Viktorin, A., Barnes, M.R., Bettecken, T., Binder, E.B., Breuer, R., Castro, V.M., Churchill, S.E., Coryell, W.H., Craddock, N., Craig, I.W., Czamara, D., Degenhardt, F., Farmer, A.E., Fava, M., Frank, J., Gainer, V.S., Gallagher, P.J., Gordon, S.D., Goryachev, S., Gross, M., Guipponi, M., Henders, A.K., Herms, S., Hickie, I.B., Hoefels, S., Hoogendijk, W., Iosifescu, D.V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J.A., Kohane, I.S., Kohli, M.A., Korszun, A., Landen, M., Lawson, W.B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P.J., McIntosh, A., McLean, A., Middeldorp, C.M., Middleton, L., Montgomery, G.M., Murphy, S.N., Nauck, M., Nolen, W.A., Nyholt, D.R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W.A., Schulz, A., Schulze, T.G., Shyn, S.I., Sigurdsson, E., Slager, S.L., Smit, J.H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Van Grootheest, G., Völzke, H., Weilburg, J.B., Willemsen, G., Zitman, F.G., Neale, B., Daly, M., Sullivan, P.F., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Allik, J., Amin, N., Attia, J.R., Bandinelli, S., Barnard, J., Bastardot, F., Baumeister, S.E., Beauchamp, J., Benjamin, D.J., Benke, K.S., Bennett, D.A., Berger, K., Bielak, L.F., Bierut, L.J., Boatman, J.A., Boyle, P.A., Bültmann, U., Campbell, H., Cesarini, D., Chabris, C.F., Cherkas, L., Chung, M.K., Conley, D., Cucca, F., Davey-Smith, G., Davies, G., de Andrade, M., De Jager, P.L., de Leeuw, C., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Derringer, J., Dimitriou, M., Eiriksdottir, G., Eklund, N., Elderson, M.F., Eriksson, J.G., Evans, D.S., Evans, D.M., Faul, J.D., Fehrmann, R., Ferrucci, L., Fischer, K., Franke, L., Garcia, M.E., Gieger, C., Gjessing, H.K., Groenen, P.J., Grönberg, H., Gudnason, V., Hägg, S., Hall, P., Harris, J.R., Harris, J.M., Harris, T.B., Hastie, N.D., Hayward, C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Holzapfel, C., Iacono, W.G., Ibrahim-Verbaas, C.A., Illig, T., Ingelsson, E., Jacobsson, B., Järvelin, M.R., Jhun, M.A., Johannesson, M., Joshi, P.K., Jugessur, A., Kaakinen, M., Kähönen, M., Kanoni, S., Kaprio, J., Kardia, S.L., Karjalainen, J., Kirkpatrick, R.M., Koellinger, P.D., Kolcic, I., Kowgier, M., Kristiansson, K., Krueger, R.F., Lahti, J., Laibson, D., Latvala, A., Launer, L.J., Lawlor, D.A., Lethimäki, T., Li, J., Lichtner, P.K., Liewald, D.C., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., Magnusson, P.K., Mäkinen, T.E., Vidal, P.M., Martin, N.W., Masala, M., McGue, M., McMahon, G., Meirelles, O., Meyer, M.N., Mielck, A., Milani, L., Miller, M.B., Montgomery, G.W., Mukherjee, S., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Oostra, B.A., Palmer, L.J., Palotie, A., Perola, M., Petrovic, K.E., Peyser, P.A., Polašek, O., Posthuma, D., Quaye, L., Räikkönen, K., Raitakari, O.T., Realo, A., Reinmaa, E., Rice, J.P., Ring, S.M., Ripatti, S., Rivadeneira, F., Rizzi, T.S., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Schmidt, H., Schmidt, R., Scott, R.J., Shakhbazov, K., Smith, A.V., Smith, J.A., Snieder, H., Pourcain, B.S., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Tanaka, T., Terracciano, A., Thurik, A.R., Tiemeier, H., Timpson, N.J., Uitterlinden, A.G., van der Loos, M.J., van Duijn, C.M., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Visscher, P.M., Vitart, V., Vollenweider, P.K., Vonk, J.M., Waeber, G., Weir, D.R., Wellmann, J., Westra, H.J., Wichmann, H.E., Widen, E., Wilson, J.F., Wright, A.F., Yang, J., Yu, L., and Zhao, W.
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Netherlands Twin Register (NTR) ,Male ,Genome-wide association study ,Logistic regression ,Cohort Studies ,Odds Ratio ,pleiotropic genetic effects ,Netherlands ,Psychiatry ,education.field_of_study ,Likelihood Functions ,Single Nucleotide ,Middle Aged ,Psychiatry and Mental health ,educational attainment ,depression ,Major depressive disorder ,Educational Status ,Regression Analysis ,Female ,Psychology ,Adult ,Estonia ,medicine.medical_specialty ,Biochemistry & Molecular Biology ,Aged ,Depressive Disorder, Major/epidemiology ,Depressive Disorder, Major/genetics ,Depressive Disorder, Major/psychology ,Estonia/epidemiology ,Gene-Environment Interaction ,Genetic Association Studies ,Genotype ,Humans ,Netherlands/epidemiology ,Polymorphism, Single Nucleotide/genetics ,Psychiatric Status Rating Scales ,Concordance ,Population ,SNP ,Single-nucleotide polymorphism ,Genetic correlation ,behavioral disciplines and activities ,Polymorphism, Single Nucleotide ,Article ,Cellular and Molecular Neuroscience ,mental disorders ,medicine ,Polymorphism ,education ,Molecular Biology ,Depressive Disorder ,Depressive Disorder, Major ,major depressive disorder ,ta1184 ,Neurosciences ,Major ,Odds ratio ,medicine.disease ,ta3124 ,Neurosciences & Neurology ,polymorphisms ,Demography - Abstract
An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed
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- 2015
16. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
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Anita Thapar, Lena Backlund, Lindsey Kent, Walter J. Muir, A. Jeremy Willsey, Sandra K. Loo, Michael Boehnke, Christa Lese Martin, Ania Korszun, Guiomar Oliveira, Veronica J. Vieland, Stephen W. Scherer, René S. Kahn, Darina Czamara, Jeremy R. Parr, Michael E. Goddard, Willem A. Nolen, Josep Antoni Ramos-Quiroga, Stephen Sanders, Karola Rehnstroem, Nelson B. Freimer, Erin N. Smith, Ann Olincy, Ingrid Melle, Myrna M. Weissman, James A. Knowles, William Byerley, Aravinda Chakravarti, Shaun Purcell, Jens Treutlein, Sebastian Zoellner, Hakon Hakonarson, Susanne Lucae, Markus M. Noethen, Ian B. Hickie, Marion Friedl, Srinivasa Thirumalai, Stephen Newhouse, Joseph Piven, Andrew M. McIntosh, Cathryn M. Lewis, Srdjan Djurovic, Francis J. McMahon, Ayman H. Fanous, Bernie Devlin, Steven A. McCarroll, Alan F. Schatzberg, Peter Szatmari, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Gerard van Grootheest, Phil Lee, Richard Anney, Elaine K. Green, Geraldine Dawson, Joseph A. Sergeant, Digby Quested, Magdalena Gross, Jack D. Barchas, Nicholas G. Martin, Timothy W. Yu, Jouke-Jan Hottenga, Mark Lathrop, Federica Tozzi, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Sandra Meier, Louise Gailagher, David A. Collier, Farooq Amin, Michael C. Neale, Martin Schalling, Lieuwe de Haan, Bru Cormand, Falk W. Lohoff, Jennifer Crosbie, Howard J. Edenberg, Aarno Palotie, Johannes H. Smit, Robert Freedman, Katherine Gordon-Smith, Michele L. Pergadia, Enda M. Byrne, Hans-Christoph Steinhausen, Benjamin M. Neale, Anjali K. Henders, Michele T. Pato, Manuel Mattheisen, Urban Ösby, Edward M. Scolnick, Evaristus A. Nwulia, Fritz Poustka, Gonneke Willemsen, Andrew C. Heath, David St. Cair, Emma M. Quinn, I. Nicol Ferrier, John R. Kelsoe, Vanessa Hus, Andrew McQuillin, John P. Rice, William M. McMahon, Joseph Biederman, Danyu Lin, Wolfgang Maier, Frans G. Zitman, Josephine Elia, Nicholas J. Schork, Stéphane Jamain, Lizzy Rossin, Jubao Duan, Ingrid Agartz, Devin Absher, Jordan W. Smoller, Matthew W. State, Richard M. Myers, Shrikant Mane, Carlos N. Pato, William E. Bunney, Marian L. Hamshere, Manfred Uhr, Nicholas John Craddock, Astrid M. Vicente, Tobias Banaschewski, David Curtis, Anne Farmer, Scott D. Gordon, Anna K. Kaehler, Eric M. Morrow, Marcella Rietschel, Patrik K. E. Magnusson, Klaus-Peter Lesch, Rebecca McKinney, Jana Strohmaier, Thomas F. Wienker, Pablo V. Gejman, Douglas Blackwood, Maria Helena Pinto de Azevedo, Tiffany A. Greenwood, Don H. Linszen, Daniel L. Koller, Richard Bruggeman, Vinay Puri, Naomi R. Wray, Stanley J. Watson, Elena Maestrini, Valentina Moskvina, Frank Dudbridge, Danielle Posthuma, Edward G. Jones, Lambertus Klei, Sarah E. Bergen, Fan Meng, Steven P. Hamilton, Guy A. Rouleau, Pierandrea Muglia, Mikael Landén, Stephanie H. Witt, Laramie E. Duncan, Stanley Zammit, Judith A. Badner, Florian Holsboer, Eco J. C. de Geus, Daniel Moreno-De-Luca, Benjamin S. Pickard, Gunnar Morken, Michael Conlon O'Donovan, Michael Steffens, Kathryn Roeder, Dorret I. Boomsma, Paul D. Shilling, Stephan Ripke, Nigel Williams, Jeremy M. Silverman, David Craig, Mark J. Daly, Michael Bauer, Detelina Grozeva, Markus J. Schwarz, Peter Holmans, Hugh Gurling, T. Scott Stroup, Aribert Rothenberger, Gary Donohoe, Eric Fombonne, Joseph D. Buxbaum, Matthew Flicldnger, Bryan J. Mowry, Thomas Hansen, Ina Giegling, Grant W. Montgomery, Caroline M. Nievergelt, Susan L. Smalley, Jung-Ying Tzeng, David H. Ledbetter, Christopher A. Walsh, Gerard D. Schellenberg, Sarah E. Medland, Robert D. Oades, James B. Potash, Dan E. Arking, Johannes Schumacher, Michael Gill, James J. McGough, Jennifer L. Moran, Donald W. Black, Sian Caesar, Neelroop N. Parikshak, Ian W. Craig, Sabine M. Klauck, Wade H. Berrettini, T. Foroud, Peter P. Zandi, Inez Myin-Germeys, Marcus Ising, Sven Cichon, Alexandre A. Todorov, Mònica Bayés, Thomas Werge, Susan L. Slager, Stanley I. Shyn, Jim van Os, Derek W. Morris, Douglas M. Ruderfer, Thomas W. Muehleisen, Matthew C. Keller, Susmita Datta, Ian Jones, John B. Vincent, James L. Kennedy, Anthony P. Monaco, Jianxin Shi, Dale R. Nyholt, Bruno Etain, Christine Fraser, Paul Cormican, Miguel Casas, Radhika Kandaswamy, Gerome Breen, Stephen V. Faraone, Jonna Kuntsi, Thomas Bettecken, Witte J.G. Hoogendijk, Nancy G. Buccola, Franziska Degenhardt, Lyudmila Georgieva, Marion Leboyer, Alan R. Sanders, John Strauss, Dan Rujescu, Russell Schachar, Helena Medeiros, Lisa Jones, Peter M. Visscher, Lauren A. Weiss, René Breuer, John I. Nurnberger, Andreas Reif, Phoenix Kwan, Vihra Milanova, Chunyu Liu, Martin A. Kohli, Donald J. MacIntyre, Nicholas Bass, Khalid Choudhury, Edwin H. Cook, Catherine Lord, Andrew D. Paterson, Jobst Meyer, Richard P. Ebstein, Zhaoming Zhao, Niklas Laengstroem, Thomas G. Schulze, Peter Propping, Wei Xu, Robert C. Thompson, Kimberly Chambert, Jonathan Pimm, Ivan Nikolov, Pamela A. F. Madden, Kevin A. McGhee, Jacob Lawrence, Jan K. Buitelaar, Andres Ingason, Christine M. Freitag, Robert Krasucki, Wiepke Cahn, Rita M. Cantor, Christina M. Hultman, Melvin G. McInnis, Catalina Betancur, Eftichia Duketis, Michael T. Murtha, Thomas H. Wassink, Philip Asherson, John S. Witte, Elaine Kenny, Edmund J.S. Sonuga-Barke, Lydia Krabbendam, Line Olsen, Agatino Battaglia, Laura J. Scott, Annette M. Hartmann, Yunjung Kim, Richard O. Day, Edwin J. C. G. van den Oord, Ole A. Andreassen, Herbert Roeyers, Michael John Owen, Colm O'Dushlaine, Peng Zhang, Morten Mattingsdal, Michael L. Cuccaro, Margaret A. Pericak-Vance, Joachim Hallmayer, Jun Li, Pamela B. Mahon, Elisabeth B. Binder, William A. Scheftner, Daniel H. Geschwind, Christel M. Middeldorp, Josef Frank, Keith Matthews, Jennifer K. Lowe, Paul Lichtenstein, Verneri Anttila, Pamela Sklar, Szabocls Szelinger, Roel A. Ophoff, Peter McGuffin, Stefan Herms, Bettina Konte, George Kirov, Hilary Coon, Maria Hipolito, Louise Frisén, Kenneth S. Kendler, Frank Bellivier, James S. Sutdiffe, Jeffrey A. Lieberman, Todd Lencz, Susanne Hoefels, Alan W. McLean, Barbara Franke, Huda Akil, Soumya Raychaudhuri, Ellen M. Wijsman, Vishwajit L. Nimgaonkar, Roy H. Perlis, Patrick J. McGrath, Susan L. Santangelo, William Coryell, Henrik B. Rasmussen, Weihua Guan, William Lawson, Elliot S. Gershon, Sean Ennis, Aiden Corvin, Allan H. Young, Thomas B. Barrett, Jonathan L. Haines, Douglas F. Levinson, Ana Miranda, Anil K. Malhotra, S. Hong Lee, Stan F. Nelson, Anthony J. Bailey, Patrick F. Sullivan, Dorothy E. Grice, Lefkos T. Middleton, Bertram Mueller-Myhsok, Michael R. Barnes, Adebayo Anjorin, O'Dushlaine, C, Rossin, L, Lee, Ph, Duncan, L, Parikshak, Nn, Newhouse, S, Ripke, S, Neale, Bm, Purcell, Sm, Posthuma, D, Nurnberger, Ji, Lee, Sh, Faraone, Sv, Perlis, Rh, Mowry, Bj, Thapar, A, Goddard, Me, Witte, J, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, Oa, Anjorin, A, Anney, R, Anttila, V, Arking, De, Asherson, P, Azevedo, Mh, Backlund, L, Badner, Ja, Bailey, Aj, Banaschewski, T, Barchas, Jd, Barnes, Mr, Barrett, Tb, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, Se, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, Eb, Black, Dw, Blackwood, Dh, Bloss, C, Boehnke, M, Boomsma, Di, Breuer, R, Bruggeman, R, Cormican, P, Buccola, Ng, Buitelaar, Jk, Bunney, We, Buxbaum, Jd, Byerley, Wf, Byrne, Em, Caesar, S, Cahn, W, Cantor, Rm, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Mattheisen, M, Cloninger, Cr, Collier, Da, Cook, Eh, Coon, H, Cormand, B, Corvin, A, Coryell, Wh, Craig, Dw, Craig, Iw, Crosbie, J, Cuccaro, Ml, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, Ej, Degenhardt, F, Djurovic, S, Donohoe, Gj, Doyle, Ae, Duan, J, Dudbridge, F, Duketis, E, Ebstein, Rp, Edenberg, Hj, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, Ae, Ferrier, In, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, Nb, Freitag, Cm, Friedl, M, Frisén, L, Gallagher, L, Gejman, Pv, Georgieva, L, Gershon, E, Giegling, I, Gill, M, Gordon, Sd, Gordon-Smith, K, Green, Ek, Greenwood, Ta, Grice, De, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, Jl, Hakonarson, H, Hallmayer, J, Hamilton, Sp, Hamshere, Ml, Hansen, Tf, Hartmann, Am, Hautzinger, M, Heath, Ac, Henders, Ak, Herms, S, Hickie, Ib, Hipolito, M, Hoefels, S, Holsboer, F, Hoogendijk, Wj, Hottenga, Jj, Hultman, Cm, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, Eg, Jones, I, Jones, L, Tzeng, Jy, Kähler, Ak, Kahn, R, Kandaswamy, R, Keller, Mc, Kennedy, Jl, Kenny, E, Kent, L, Kim, Y, Kirov, Gk, Klauck, Sm, Klei, L, Knowles, Ja, Kohli, Ma, Koller, Dl, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landén, M, Längström, N, Lathrop, M, Lawrence, J, Lawson, Wb, Leboyer, M, Ledbetter, Dh, Lencz, T, Lesch, Kp, Levinson, Df, Lewis, Cm, Li, J, Lichtenstein, P, Lieberman, Ja, Lin, Dy, Linszen, Dh, Liu, C, Lohoff, Fw, Loo, Sk, Lord, C, Lowe, Jk, Lucae, S, Macintyre, Dj, Madden, Pa, Maestrini, E, Magnusson, Pk, Mahon, Pb, Maier, W, Malhotra, Ak, Mane, Sm, Martin, Cl, Martin, Ng, Matthews, K, Mattingsdal, M, Mccarroll, Sa, Mcghee, Ka, Mcgough, Jj, Mcgrath, Pj, Mcguffin, P, Mcinnis, Mg, Mcintosh, A, Mckinney, R, Mclean, Aw, Mcmahon, Fj, Mcmahon, Wm, Mcquillin, A, Medeiros, H, Medland, Se, Meier, S, Melle, I, Meyer, J, Middeldorp, Cm, Middleton, L, Milanova, V, Miranda, A, Monaco, A, Montgomery, Gw, Moran, Jl, Moreno-De-Luca, D, Morken, G, Morris, Dw, Morrow, Em, Moskvina, V, Muglia, P, Mühleisen, Tw, Muir, Wj, Müller-Myhsok, B, Murtha, M, Myers, Rm, Myin-Germeys, I, Neale, Mc, Nelson, Sf, Nievergelt, Cm, Nikolov, I, Nimgaonkar, V, Nolen, Wa, Nöthen, Mm, Nwulia, Ea, Nyholt, Dr, Oades, Rd, Olincy, A, Oliveira, G, Olsen, L, Ophoff, Ra, Osby, U, Owen, Mj, Palotie, A, Parr, Jr, Paterson, Ad, Pato, Cn, Pato, Mt, Penninx, Bw, Pergadia, Ml, Pericak-Vance, Ma, Pickard, B, Pimm, J, Piven, J, Potash, Jb, Poustka, F, Propping, P, Puri, V, Quested, Dj, Quinn, Em, Ramos-Quiroga, Ja, Rasmussen, Hb, Raychaudhuri, S, Rehnström, K, Reif, A, Ribasés, M, Rice, Jp, Rietschel, M, Roeder, K, Roeyers, H, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, Ar, Sanders, Sj, Santangelo, Sl, Sergeant, Ja, Schachar, R, Schalling, M, Schatzberg, Af, Scheftner, Wa, Schellenberg, Gd, Scherer, Sw, Schork, Nj, Schulze, Tg, Schumacher, J, Schwarz, M, Scolnick, E, Scott, Lj, Shi, J, Shilling, Pd, Shyn, Si, Silverman, Jm, Slager, Sl, Smalley, Sl, Smit, Jh, Smith, En, Sonuga-Barke, Ej, St Clair, D, State, M, Steffens, M, Steinhausen, Hc, Strauss, J, Strohmaier, J, Stroup, T, Sutcliffe, J, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, Rc, Todorov, Aa, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, Jc, Van Grootheest, G, Van Os, J, Vicente, A, Vieland, Vj, Vincent, Jb, Visscher, Pm, Walsh, Ca, Wassink, Th, Watson, Sj, Weissman, Mm, Werge, T, Wienker, Tf, Wijsman, Em, Willemsen, G, Williams, N, Willsey, Aj, Witt, Sh, Xu, W, Young, Ah, Yu, Tw, Zammit, S, Zandi, Pp, Zhang, P, Zitman, Fg, Zöllner, S, Devlin, B, Kelsoe, Jr, Sklar, P, Daly, Mj, O'Donovan, Mc, Craddock, N, Kendler, K, Weiss, La, Wray, Nr, Zhao, Z, Geschwind, Dh, Sullivan, Pf, Smoller, Jw, Holmans, Pa, Breen, G., Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Human genetics, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Gastroenterology & Hepatology, Hematology, University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), RS: MHeNs - R2 - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Universitat de Barcelona, Perceptual and Cognitive Neuroscience (PCN), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Complex Trait Genetics, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, LEARN! - Brain, learning and development, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Lee, S Hong, Breen, Gerome, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, and Myin-Germeys, Inez
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Netherlands Twin Register (NTR) ,Statistical methods ,Autism ,Medizin ,LOCI ,Genome-wide association study ,heritability ,Genome-wide association studies ,Histones ,Genètica mèdica ,0302 clinical medicine ,Histone methylation ,Databases, Genetic ,2.1 Biological and endogenous factors ,Psychology ,GWAS ,Aetiology ,Psychiatric genetics ,R2C ,bipolar disorder ,Psychiatry ,0303 health sciences ,Disorders ,Loci ,Depression ,General Neuroscience ,Mental Disorders ,Medical genetics ,METHYLATION ,Brain ,3rd-DAS ,Serious Mental Illness ,Psychiatric Disorders ,3. Good health ,Histone ,Mental Health ,Schizophrenia ,Mental Disorder ,Cognitive Sciences ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Promoters ,BDC ,BURDEN ,RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry ,Human ,Signal Transduction ,medicine.medical_specialty ,DISORDERS ,Genomics ,Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium ,Burden ,Biology ,Methylation ,Article ,Biological pathway ,PROMOTERS ,03 medical and health sciences ,Databases ,Genetic ,medicine ,Genetics ,Humans ,Genetic Predisposition to Disease ,histone methylation ,Bipolar disorder ,Psiquiatria ,AUTISM ,030304 developmental biology ,Genetic association ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Neurology & Neurosurgery ,Neuroscience (all) ,Human Genome ,Neurosciences ,medicine.disease ,Brain Disorders ,Good Health and Well Being ,DE-NOVO MUTATIONS ,Perturbações do Desenvolvimento Infantil e Saúde Mental ,RC0321 ,Genome-wide Association Studies ,De-novo mutations ,major depression ,Neuroscience ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. Postprint
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- 2015
17. Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
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Robert Maier, Gerhard Moser, Guo-Bo Chen, Stephan Ripke, William Coryell, James B. Potash, William A. Scheftner, Jianxin Shi, Myrna M. Weissman, Christina M. Hultman, Mikael Landén, Douglas F. Levinson, Kenneth S. Kendler, Jordan W. Smoller, Naomi R. Wray, S. Hong Lee, Devin Absher, Ingrid Agartz, Huda Akil, Farooq Amin, Ole A. Andreassen, Adebayo Anjorin, Richard Anney, Dan E. Arking, Philip Asherson, Maria H. Azevedo, Lena Backlund, Judith A. Badner, Anthony J. Bailey, Tobias Banaschewski, Jack D. Barchas, Michael R. Barnes, Thomas B. Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E. Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B. Binder, Donald W. Black, Douglas H.R. Blackwood, Cinnamon S. Bloss, Michael Boehnke, Dorret I. Boomsma, Gerome Breen, René Breuer, Richard Bruggeman, Nancy G. Buccola, Jan K. Buitelaar, William E. Bunney, Joseph D. Buxbaum, William F. Byerley, Sian Caesar, Wiepke Cahn, Rita M. Cantor, Miguel Casas, Aravinda Chakravarti, Kimberly Chambert, Khalid Choudhury, Sven Cichon, C. Robert Cloninger, David A. Collier, Edwin H. Cook, Hilary Coon, Bru Cormand, Paul Cormican, Aiden Corvin, William H. Coryell, Nicholas Craddock, David W. Craig, Ian W. Craig, Jennifer Crosbie, Michael L. Cuccaro, David Curtis, Darina Czamara, Mark J. Daly, Susmita Datta, Geraldine Dawson, Richard Day, Eco J. De Geus, Franziska Degenhardt, Bernie Devlin, Srdjan Djurovic, Gary J. Donohoe, Alysa E. Doyle, Jubao Duan, Frank Dudbridge, Eftichia Duketis, Richard P. Ebstein, Howard J. Edenberg, Josephine Elia, Sean Ennis, Bruno Etain, Ayman Fanous, Stephen V. Faraone, Anne E. Farmer, I. Nicol Ferrier, Matthew Flickinger, Eric Fombonne, Tatiana Foroud, Josef Frank, Barbara Franke, Christine Fraser, Robert Freedman, Nelson B. Freimer, Christine M. Freitag, Marion Friedl, Louise Frisén, Louise Gallagher, Pablo V. Gejman, Lyudmila Georgieva, Elliot S. Gershon, Daniel H. Geschwind, Ina Giegling, Michael Gill, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Tiffany A. Greenwood, Dorothy E. Grice, Magdalena Gross, Detelina Grozeva, Weihua Guan, Hugh Gurling, Lieuwe De Haan, Jonathan L. Haines, Hakon Hakonarson, Joachim Hallmayer, Steven P. Hamilton, Marian L. Hamshere, Thomas F. Hansen, Annette M. Hartmann, Martin Hautzinger, Andrew C. Heath, Anjali K. Henders, Stefan Herms, Ian B. Hickie, Maria Hipolito, Susanne Hoefels, Peter A. Holmans, Florian Holsboer, Witte J. Hoogendijk, Jouke-Jan Hottenga, Vanessa Hus, Andrés Ingason, Marcus Ising, Stéphane Jamain, Ian Jones, Lisa Jones, Anna K. Kähler, René S. Kahn, Radhika Kandaswamy, Matthew C. Keller, John R. Kelsoe, James L. Kennedy, Elaine Kenny, Lindsey Kent, Yunjung Kim, George K. Kirov, Sabine M. Klauck, Lambertus Klei, James A. Knowles, Martin A. Kohli, Daniel L. Koller, Bettina Konte, Ania Korszun, Lydia Krabbendam, Robert Krasucki, Jonna Kuntsi, Phoenix Kwan, Niklas Långström, Mark Lathrop, Jacob Lawrence, William B. Lawson, Marion Leboyer, David H. Ledbetter, Phil H. Lee, Todd Lencz, Klaus-Peter Lesch, Cathryn M. Lewis, Jun Li, Paul Lichtenstein, Jeffrey A. Lieberman, Dan-Yu Lin, Don H. Linszen, Chunyu Liu, Falk W. Lohoff, Sandra K. Loo, Catherine Lord, Jennifer K. Lowe, Susanne Lucae, Donald J. MacIntyre, Pamela A.F. Madden, Elena Maestrini, Patrik K.E. Magnusson, Pamela B. Mahon, Wolfgang Maier, Anil K. Malhotra, Shrikant M. Mane, Christa L. Martin, Nicholas G. Martin, Manuel Mattheisen, Keith Matthews, Morten Mattingsdal, Steven A. McCarroll, Kevin A. McGhee, James J. McGough, Patrick J. McGrath, Peter McGuffin, Melvin G. McInnis, Andrew McIntosh, Rebecca McKinney, Alan W. McLean, Francis J. McMahon, William M. McMahon, Andrew McQuillin, Helena Medeiros, Sarah E. Medland, Sandra Meier, Ingrid Melle, Fan Meng, Jobst Meyer, Christel M. Middeldorp, Lefkos Middleton, Vihra Milanova, Ana Miranda, Anthony P. Monaco, Grant W. Montgomery, Jennifer L. Moran, Daniel Moreno-De-Luca, Gunnar Morken, Derek W. Morris, Eric M. Morrow, Valentina Moskvina, Bryan J. Mowry, Pierandrea Muglia, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael Murtha, Richard M. Myers, Inez Myin-Germeys, Benjamin M. Neale, Stan F. Nelson, Caroline M. Nievergelt, Ivan Nikolov, Vishwajit Nimgaonkar, Willem A. Nolen, Markus M. Nöthen, John I. Nurnberger, Evaristus A. Nwulia, Dale R. Nyholt, Michael C. O’Donovan, Colm O’Dushlaine, Robert D. Oades, Ann Olincy, Guiomar Oliveira, Line Olsen, Roel A. Ophoff, Urban Osby, Michael J. Owen, Aarno Palotie, Jeremy R. Parr, Andrew D. Paterson, Carlos N. Pato, Michele T. Pato, Brenda W. Penninx, Michele L. Pergadia, Margaret A. Pericak-Vance, Roy H. Perlis, Benjamin S. Pickard, Jonathan Pimm, Joseph Piven, Danielle Posthuma, Fritz Poustka, Peter Propping, Shaun M. Purcell, Vinay Puri, Digby J. Quested, Emma M. Quinn, Josep Antoni Ramos-Quiroga, Henrik B. Rasmussen, Soumya Raychaudhuri, Karola Rehnström, Andreas Reif, Marta Ribasés, John P. Rice, Marcella Rietschel, Kathryn Roeder, Herbert Roeyers, Lizzy Rossin, Aribert Rothenberger, Guy Rouleau, Douglas Ruderfer, Dan Rujescu, Alan R. Sanders, Stephan J. Sanders, Susan L. Santangelo, Russell Schachar, Martin Schalling, Alan F. Schatzberg, Gerard D. Schellenberg, Stephen W. Scherer, Nicholas J. Schork, Thomas G. Schulze, Johannes Schumacher, Markus Schwarz, Edward Scolnick, Laura J. Scott, Joseph A. Sergeant, Paul D. Shilling, Stanley I. Shyn, Jeremy M. Silverman, Pamela Sklar, Susan L. Slager, Susan L. Smalley, Johannes H. Smit, Erin N. Smith, Edmund J.S. Sonuga-Barke, David St Clair, Matthew State, Michael Steffens, Hans-Christoph Steinhausen, John S. Strauss, Jana Strohmaier, T. Scott Stroup, Patrick F. Sullivan, James Sutcliffe, Peter Szatmari, Szabocls Szelinger, Anita Thapar, Srinivasa Thirumalai, Robert C. Thompson, Alexandre A. Todorov, Federica Tozzi, Jens Treutlein, Jung-Ying Tzeng, Manfred Uhr, Edwin J.C.G. van den Oord, Gerard Van Grootheest, Jim Van Os, Astrid M. Vicente, Veronica J. Vieland, John B. Vincent, Peter M. Visscher, Christopher A. Walsh, Thomas H. Wassink, Stanley J. Watson, Lauren A. Weiss, Thomas Werge, Thomas F. Wienker, Durk Wiersma, Ellen M. Wijsman, Gonneke Willemsen, Nigel Williams, A. Jeremy Willsey, Stephanie H. Witt, Wei Xu, Allan H. Young, Timothy W. Yu, Stanley Zammit, Peter P. Zandi, Peng Zhang, Frans G. Zitman, Sebastian Zöllner, University of Zurich, Lee, S Hong, Epidemiology and Data Science, Psychiatry, EMGO - Mental health, NCA - Neurobiology of mental health, Human genetics, NCA - Brain mechanisms in health and disease, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Maier, Robert, Moser, Gerhard, Chen, Guo-Bo, Ripke, Stephan, Coryell, William, Potash, James B, Scheftner, William A, Shi, Jianxin, Weissman, Myrna M, Hultman, Christina M, Landen, Mikael, Levinson, Douglas F, Kendler, Kenneth S, Smoller, Jordan, Wray, Naomi R, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Oades, Robert D. (Beitragende*r), Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Maier R., Moser G., Chen G.-B., Ripke S., Coryell W., Potash J.B., Scheftner W.A., Shi J., Weissman M.M., Hultman C.M., Landen M., Levinson D.F., Kendler K.S., Smoller J.W., Wray N.R., Lee S.H., Absher D., Agartz I., Akil H., Amin F., Andreassen O.A., Anjorin A., Anney R., Arking D.E., Asherson P., Azevedo M.H., Backlund L., Badner J.A., Bailey A.J., Banaschewski T., Barchas J.D., Barnes M.R., Barrett T.B., Bass N., Battaglia A., Bauer M., Bayes M., Bellivier F., Bergen S.E., Berrettini W., Betancur C., Bettecken T., Biederman J., Binder E.B., Black D.W., Blackwood D.H.R., Bloss C.S., Boehnke M., Boomsma D.I., Breen G., Breuer R., Bruggeman R., Buccola N.G., Buitelaar J.K., Bunney W.E., Buxbaum J.D., Byerley W.F., Caesar S., Cahn W., Cantor R.M., Casas M., Chakravarti A., Chambert K., Choudhury K., Cichon S., Robert Cloninger C., Collier D.A., Cook E.H., Coon H., Cormand B., Cormican P., Corvin A., Coryell W.H., Craddock N., Craig D.W., Craig I.W., Crosbie J., Cuccaro M.L., Curtis D., Czamara D., Daly M.J., Datta S., Dawson G., Day R., De Geus E.J., Degenhardt F., Devlin B., Djurovic S., Donohoe G.J., Doyle A.E., Duan J., Dudbridge F., Duketis E., Ebstein R.P., Edenberg H.J., Elia J., Ennis S., Etain B., Fanous A., Faraone S.V., Farmer A.E., Nicol Ferrier I., Flickinger M., Fombonne E., Foroud T., Frank J., Franke B., Fraser C., Freedman R., Freimer N.B., Freitag C.M., Friedl M., Frisen L., Gallagher L., Gejman P.V., Georgieva L., Gershon E.S., Geschwind D.H., Giegling I., Gill M., Gordon S.D., Gordon-Smith K., Green E.K., Greenwood T.A., Grice D.E., Gross M., Grozeva D., Guan W., Gurling H., De Haan L., Haines J.L., Hakonarson H., Hallmayer J., Hamilton S.P., Hamshere M.L., Hansen T.F., Hartmann A.M., Hautzinger M., Heath A.C., Henders A.K., Herms S., Hickie I.B., Hipolito M., Hoefels S., Holmans P.A., Holsboer F., Hoogendijk W.J., Hottenga J.-J., Hus V., Ingason A., Ising M., Jamain S., Jones I., Jones L., Kahler A.K., Kahn R.S., Kandaswamy R., Keller M.C., Kelsoe J.R., Kennedy J.L., Kenny E., Kent L., Kim Y., Kirov G.K., Klauck S.M., Klei L., Knowles J.A., Kohli M.A., Koller D.L., Konte B., Korszun A., Krabbendam L., Krasucki R., Kuntsi J., Kwan P., Langstrom N., Lathrop M., Lawrence J., Lawson W.B., Leboyer M., Ledbetter D.H., Lee P.H., Lencz T., Lesch K.-P., Lewis C.M., Li J., Lichtenstein P., Lieberman J.A., Lin D.-Y., Linszen D.H., Liu C., Lohoff F.W., Loo S.K., Lord C., Lowe J.K., Lucae S., MacIntyre D.J., Madden P.A.F., Maestrini E., Magnusson P.K.E., Mahon P.B., Maier W., Malhotra A.K., Mane S.M., Martin C.L., Martin N.G., Mattheisen M., Matthews K., Mattingsdal M., McCarroll S.A., McGhee K.A., McGough J.J., McGrath P.J., McGuffin P., McInnis M.G., McIntosh A., McKinney R., McLean A.W., McMahon F.J., McMahon W.M., McQuillin A., Medeiros H., Medland S.E., Meier S., Melle I., Meng F., Meyer J., Middeldorp C.M., Middleton L., Milanova V., Miranda A., Monaco A.P., Montgomery G.W., Moran J.L., Moreno-De-Luca D., Morken G., Morris D.W., Morrow E.M., Moskvina V., Mowry B.J., Muglia P., Muhleisen T.W., Muller-Myhsok B., Murtha M., Myers R.M., Myin-Germeys I., Neale B.M., Nelson S.F., Nievergelt C.M., Nikolov I., Nimgaonkar V., Nolen W.A., Nothen M.M., Nurnberger J.I., Nwulia E.A., Nyholt D.R., O'Donovan M.C., O'Dushlaine C., Oades R.D., Olincy A., Oliveira G., Olsen L., Ophoff R.A., Osby U., Owen M.J., Palotie A., Parr J.R., Paterson A.D., Pato C.N., Pato M.T., Penninx B.W., Pergadia M.L., Pericak-Vance M.A., Perlis R.H., Pickard B.S., Pimm J., Piven J., Posthuma D., Poustka F., Propping P., Purcell S.M., Puri V., Quested D.J., Quinn E.M., Ramos-Quiroga J.A., Rasmussen H.B., Raychaudhuri S., Rehnstrom K., Reif A., Ribases M., Rice J.P., Rietschel M., Roeder K., Roeyers H., Rossin L., Rothenberger A., Rouleau G., Ruderfer D., Rujescu D., Sanders A.R., Sanders S.J., Santangelo S.L., Schachar R., Schalling M., Schatzberg A.F., Schellenberg G.D., Scherer S.W., Schork N.J., Schulze T.G., Schumacher J., Schwarz M., Scolnick E., Scott L.J., Sergeant J.A., Shilling P.D., Shyn S.I., Silverman J.M., Sklar P., Slager S.L., Smalley S.L., Smit J.H., Smith E.N., Sonuga-Barke E.J.S., St Clair D., State M., Steffens M., Steinhausen H.-C., Strauss J.S., Strohmaier J., Scott Stroup T., Sullivan P.F., Sutcliffe J., Szatmari P., Szelinger S., Thapar A., Thirumalai S., Thompson R.C., Todorov A.A., Tozzi F., Treutlein J., Tzeng J.-Y., Uhr M., van den Oord E.J.C.G., Van Grootheest G., Van Os J., Vicente A.M., Vieland V.J., Vincent J.B., Visscher P.M., Walsh C.A., Wassink T.H., Watson S.J., Weiss L.A., Werge T., Wienker T.F., Wiersma D., Wijsman E.M., Willemsen G., Williams N., Jeremy Willsey A., Witt S.H., Xu W., Young A.H., Yu T.W., Zammit S., Zandi P.P., Zhang P., Zitman F.G., and Zollner S.
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Netherlands Twin Register (NTR) ,Multifactorial Inheritance ,Multivariate analysis ,Bipolar Disorder ,genome annotation ,Medizin ,R Medicine (General) ,Medical and Health Sciences ,Genome-wide association studies ,0302 clinical medicine ,2.5 Research design and methodologies (aetiology) ,GWAS ,Genetics(clinical) ,Aetiology ,Multivariate Analysi ,Genetics (clinical) ,Genetics & Heredity ,bipolar disorder ,0303 health sciences ,education.field_of_study ,Depression ,Mental Disorders ,Single Nucleotide ,3rd-DAS ,Biological Sciences ,10058 Department of Child and Adolescent Psychiatry ,Serious Mental Illness ,Psychiatric Disorders ,3. Good health ,Mental Health ,Schizophrenia ,Mental Disorder ,Linear Model ,Major depressive disorder ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Risk assessment ,Human ,medicine.medical_specialty ,2716 Genetics (clinical) ,Genetics, Medical ,Population ,SNP ,610 Medicine & health ,QH426 Genetics ,Best linear unbiased prediction ,Polymorphism, Single Nucleotide ,Risk Assessment ,03 medical and health sciences ,1311 Genetics ,Medical ,Report ,medicine ,Genetics ,Humans ,Bipolar disorder ,Genetic Testing ,Polymorphism ,education ,Psychiatry ,QH426 ,030304 developmental biology ,Depressive Disorder ,Depressive Disorder, Major ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,business.industry ,Cross-Disorder Working Group of the Psychiatric Genomics Consortium ,Prevention ,Human Genome ,Major ,medicine.disease ,genetic risk prediction ,R1 ,Brain Disorders ,schizophrenia ,Sample size determination ,Perturbações do Desenvolvimento Infantil e Saúde Mental ,Multivariate Analysis ,Linear Models ,business ,depressive disorders ,030217 neurology & neurosurgery - Abstract
Cross-Disorder Working Group of the Psychiatric Genomics Consortium - Vicente A.M. Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25640677/ Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk
- Published
- 2015
18. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
- Author
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Laura J. Scott, Bernie Devlin, Steven A. McCarroll, James S. Sutcliffe, Stefan Herms, Yunjung Kim, Richard O. Day, Thomas F. Wienker, Frank Dudbridge, I. Nicol Ferrier, Bettina Konte, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Detelina Grozeva, Herbert Roeyers, Peter Holmans, Colm O'Dushlaine, Scott D. Gordon, Sarah E. Bergen, Fan Meng, Morten Mattingsdal, Hugh Gurling, Ina Giegling, Gerard van Grootheest, Ania Korszun, Markus J. Schwarz, George Kirov, Sebastian Zöllner, Kenneth S. Kendler, Nicholas G. Martin, Michael Conlon O'Donovan, Michael C. Neale, Jim van Os, Aravinda Chakravarti, Timothy W. Yu, Mikael Landén, Inez Myin-Germeys, Markus M. Nöthen, Kathryn Roeder, James B. Potash, Alan W. McLean, Louise Gallagher, Anna K. Kähler, Thomas Bettecken, Nigel Williams, Frank Bellivier, Joseph D. Buxbaum, Derek W. Morris, Susan L. Smalley, Jung-Ying Tzeng, Martin Schalling, Douglas M. Ruderfer, Caroline M. Nievergelt, T. Scott Stroup, David H. Ledbetter, Jennifer Crosbie, Anita Thapar, Barbara Franke, Jeffrey A. Lieberman, Huda Akil, Miguel Casas, Daniel H. Geschwind, Paul Cormican, Bertram Müller-Myhsok, Lyudmila Georgieva, Robert Krasucki, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Gerard D. Schellenberg, Todd Lencz, Melvin G. McInnis, Catalina Betancur, Josep Antoni Ramos-Quiroga, Stephen Sanders, Eftichia Duketis, Don H. Linszen, Matthew W. State, Richard M. Myers, Soumya Raychaudhuri, Lizzy Rossin, Howard J. Edenberg, Michael E. Goddard, S. Hong Lee, Elisabeth B. Binder, Pablo V. Gejman, William A. Scheftner, Wolfgang Maier, Judith A. Badner, Christel M. Middeldorp, Maria Helena Pinto de Azevedo, Johannes H. Smit, Willem A. Nolen, Lieuwe de Haan, Gonneke Willemsen, Keith Matthews, Ellen M. Wijsman, Jennifer K. Lowe, Rebecca McKinney, Magdalena Gross, Dorothy E. Grice, James A. Knowles, Andrew C. Heath, Jana Strohmaier, Vishwajit L. Nimgaonkar, William Byerley, William E. Bunney, Dan E. Arking, Andrew McQuillin, William M. McMahon, Manuel Mattheisen, Hans-Christoph Steinhausen, Joseph Biederman, Guy A. Rouleau, James J. McGough, Sian Caesar, Edward M. Scolnick, Lefkos T. Middleton, Jack D. Barchas, Ian B. Hickie, Danyu Lin, Patrik K. E. Magnusson, Douglas Blackwood, Francis J. McMahon, Ingrid Agartz, Elena Maestrini, Marian L. Hamshere, Lindsey Kent, Walter J. Muir, Stephan Ripke, Lydia Krabbendam, Christine Fraser, Maria Hipolito, Louise Frisén, Eric Fombonne, Emma M. Quinn, Michael Bauer, Richard P. Ebstein, Michael Steffens, Jordan W. Smoller, Stanley J. Watson, Michael Boehnke, Philip Asherson, Agatino Battaglia, Elliot S. Gershon, Russell Schachar, Marcus Ising, Peng Zhang, Margaret A. Pericak-Vance, Joachim Hallmayer, Sean Ennis, Radhika Kandaswamy, René S. Kahn, Susanne Hoefels, Thomas W. Mühleisen, Pamela Sklar, Paul Lichtenstein, Verneri Anttila, Michael L. Cuccaro, Florian Holsboer, René Breuer, Eric M. Morrow, Vinay Puri, Naomi R. Wray, Szabocls Szelinger, Sabine M. Klauck, John B. Vincent, Shrikant Mane, Aribert Rothenberger, Marion Friedl, Ian Jones, Khalid Choudhury, Michael R. Barnes, Adebayo Anjorin, Edwin H. Cook, William Lawson, Allan H. Young, Lambertus Klei, Bryan J. Mowry, Johannes Schumacher, Michael Gill, James L. Kennedy, Marcella Rietschel, Aiden Corvin, Henrik B. Rasmussen, Susmita Datta, Kimberly Chambert, Daniel Moreno-De-Luca, Benjamin S. Pickard, Stan F. Nelson, Veronica J. Vieland, Stephen W. Scherer, Peter M. Visscher, John Strauss, Andreas Reif, Andrew D. Paterson, Ann Olincy, Phoenix Kwan, Anthony J. Bailey, Patrick F. Sullivan, Pierandrea Muglia, Gunnar Morken, Susanne Lucae, Ayman H. Fanous, Jacob Lawrence, Donald J. MacIntyre, Nancy G. Buccola, Rita M. Cantor, Christina M. Hultman, Weihua Guan, Anthony P. Monaco, Jouke-Jan Hottenga, Elaine Kenny, Jianxin Shi, Dale R. Nyholt, Kevin A. McGhee, Falk W. Lohoff, Jonna Kuntsi, Niklas Långström, John I. Nurnberger, Nelson B. Freimer, Erin N. Smith, John P. Rice, Michael T. Murtha, Thomas H. Wassink, Alexandre A. Todorov, Edmund J.S. Sonuga-Barke, Dan Rujescu, Roy H. Perlis, John S. Witte, Christopher A. Walsh, Matthew C. Keller, Pamela B. Mahon, Patrick J. McGrath, Susan L. Santangelo, Annette M. Hartmann, Ole A. Andreassen, Tatiana Foroud, Shaun Purcell, Josef Frank, Douglas F. Levinson, William Coryell, Ana Miranda, Alan F. Schatzberg, Peter Szatmari, Jun Li, Gerome Breen, Stephen V. Faraone, Anil K. Malhotra, Helena Medeiros, Martin A. Kohli, Nicholas Bass, Catherine Lord, Peter Propping, Wei Xu, Federica Tozzi, Ivan Nikolov, Jan K. Buitelaar, Thomas G. Schulze, Katherine Gordon-Smith, Michele L. Pergadia, Fritz Poustka, Valentina Moskvina, David Curtis, Tobias Banaschewski, Devin Absher, Danielle Posthuma, Stanley Zammit, Gary Donohoe, Ingrid Melle, Karola Rehnström, Thomas Hansen, Myrna M. Weissman, Stanley I. Shyn, Hakon Hakonarson, Christa Lese Martin, Digby Quested, Darina Czamara, Jeremy R. Parr, Pamela A. F. Madden, Jens Treutlein, Aarno Palotie, Robert Freedman, Sandra Meier, Bru Cormand, Nicholas J. Schork, Michele T. Pato, John R. Kelsoe, Vanessa Hus, Frans G. Zitman, Josephine Elia, David St Clair, Roel A. Ophoff, Peter McGuffin, Jonathan Pimm, Jonathan L. Haines, Wiepke Cahn, Matthew Flickinger, Steven P. Hamilton, Michael John Owen, Paul D. Shilling, Jeremy M. Silverman, David Craig, Mark J. Daly, Sarah E. Medland, Robert D. Oades, Marion Leboyer, Alan R. Sanders, Vihra Milanova, Chunyu Liu, Jobst Meyer, Dorret I. Boomsma, Evaristus A. Nwulia, Thomas B. Barrett, Jennifer L. Moran, Donald W. Black, Mònica Bayés, Witte J.G. Hoogendijk, Franziska Degenhardt, Benjamin M. Neale, Daniel L. Koller, Carlos N. Pato, Nicholas John Craddock, Richard Bruggeman, Enda M. Byrne, Edward G. Jones, Eco J. C. de Geus, Stéphane Jamain, Jubao Duan, Anne Farmer, Astrid M. Vicente, Grant W. Montgomery, Thomas Werge, Cathryn M. Lewis, Srdjan Djurovic, Phil Lee, Richard Anney, Elaine K. Green, Wade H. Berrettini, Peter P. Zandi, Susan L. Slager, Stephanie H. Witt, Ian W. Craig, Lisa Jones, Sven Cichon, Bruno Etain, Mark Lathrop, Hilary Coon, Robert C. Thompson, Lena Backlund, A. Jeremy Willsey, Andres Ingason, Christine M. Freitag, Sandra K. Loo, Guiomar Oliveira, Line Olsen, Edwin J. C. G. van den Oord, Geraldine Dawson, Joseph A. Sergeant, David A. Collier, Farooq Amin, Srinivasa Thirumalai, Manfred Uhr, Joseph Piven, Andrew M. McIntosh, Anjali K. Henders, Urban Ösby, Klaus-Peter Lesch, Tiffany A. Greenwood, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Lee, S Hong, Ripke, Stephan, Neale, Benjamin M, Faraone, Stephen V, Wray, Naomi R, Cross-Disorder Group of the Psychiatric Genomics Consortium, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Queensland Brain Institute, University of Queensland [Brisbane], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], SUNY Upstate Medical University, State University of New York (SUNY), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Psychiatric and Neurodevelopmental Genetics Unit, Queensland Centre for Mental Health Research, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], New South Wales Department of Primary Industries (NSW DPI), Faculty of Land and Food Resources, University of Melbourne, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Diakonhjemmet Hospital, University of Michigan [Ann Arbor], University of Michigan System, Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan System-University of Michigan System, Emory University [Atlanta, GA], Oslo University Hospital [Oslo], University College of London [London] (UCL), Trinity College Dublin, Johns Hopkins University School of Medicine [Baltimore], MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King's College London, University of Coimbra [Portugal] (UC), Karolinska Institutet [Stockholm], University of Chicago, University of British Columbia (UBC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Weill Medical College of Cornell University [New York], GlaxoSmithKline, Glaxo Smith Kline, Portland Veterans Administration Medical Center, Windeyer Institute for Medical Sciences, IRCCS Fondazione Stella Maris [Pisa], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Department of Psychiatry [Philadelphia], University of Pennsylvania, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Massachusetts General Hospital [Boston, MA, USA], University of Iowa [Iowa City], University of Edinburgh, Royal Hospital for Sick Children [Edinburgh], The Scripps Research Institute [La Jolla, San Diego], MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Institute of Medical Sciences, University of Aberdeen, Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, Department of Psychiatry, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Trinity College Dublin-St. James's Hospital, School of Nursing, Louisiana State University (LSU), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Department of Psychiatry and Human Behavior, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Department of Neuroscience, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Friedman Brain Institute, The Mindich Child Health and Development Institute, University of California [San Francisco] (UC San Francisco), Department of Psychiatry, School of Clinical and Experimental Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Mental Health Sciences Unit, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Developmental Neuroscience, Neuropsychiatric Genetics Research Group, University of California [San Diego] (UC San Diego), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], East London NHS Foundation Trust, Queen Mary University of London (QMUL), Max-Planck-Institut für Psychiatrie, Genetics Institute, Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Medstar Research Institute, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry and Behavioral Sciences, University of Chicago-NorthShore University Health System, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Psychology Department, National University of Singapore (NUS), Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University (VCU), University of Dundee School of Medicine, University of Dundee, Department of Biostatistics and Center for Statistical Genetics, University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), Howard University College of Medicine, University of Colorado [Denver], Center for Neurobehavioral Genetics, Department of Genomics, Department of Molecular Medicine, Department of Neurology, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Medical Research Council-Cardiff University, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Institute for Human Genetics, Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Clinical and Developmental Psychology, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Functional Genomics, Neuronal Plasticity / Mouse Behaviour, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Medical Epidemiology and Biostatistics (MEB), Autism and Communicative Disorders Centre, Center for Human Genetic Research, Center for neuroscience-University of California [Davis] (UC Davis), Bioinformatics Research Center, North Carolina State University [Raleigh] (NC State), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Emory University [Atlanta, GA]-Atlanta Veterans Affairs Medical Center, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Medicine, University of St Andrews [Scotland], Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Ecology and Evolutionary Biology, Insitute of Neuroscience and Physiology, University of Gothenburg (GU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Developmental Brain and Behaviour Unit, University of Southampton, Division of Psychiatric Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Statistical Genetics Group, Department of Human Genetics, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry and Psychotherapy, Department of Mental Health, Johns Hopkins University and Hospital, W.M. Keck Biotechnology Resource Laboratory, Yale University [New Haven], Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Genetic Epidemiology Unit, Queensland Institute of Medical Research, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Sorlandet Hospital HF, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Medical Genetics Section, University of Edinburgh-Western General Hospital, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Division of Mental Health and Addiction, Molecular Psychiatry Laboratory, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Research and Development, First Psychiatric Clinic-Alexander University Hospital, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, St. Olav's Hospital, Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Human Genetics Department, University of Pittsburgh (PITT), Institute for Biomedical Imaging and Life Science, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Carolina Institute for Developmental Disabilities, Analytic and Translational Genetics Unit, Rush University Medical Center [Chicago], Julius-Maximilians-Universität Würzburg (JMU), Washington University in Saint Louis (WUSTL), Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Department of Experimental Clinical and Health Psychology, Universiteit Gent = Ghent University (UGENT), Department of Child and Adolescent Psychiatry, Georg-August-University = Georg-August-Universität Göttingen, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Departments of Psychiatry and Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Maine Medical Center, Free University of Amsterdam, Department of Psychiatry and Behavioral Sciences [Stanford], Pathology and Laboratory Medicine, The Scripps Translational Science Institute and The Scripps Research Institute, Psychiatric Center Nordbaden, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), The Scripps Translational Science Institute and Scripps Health, Child and Adolescent Psychiatry, Aarhus University Hospital, Molecular Neuropsychiatry and Development Laboratory, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Translational Genomics Research Institute (TGen), Oxford Health NHS Foundation Trust, Marlborough House Secure Unit, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, University of Toronto, Diamantina Institute, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, University of Washington [Seattle], ArcelorMittal Maizières Research SA, ArcelorMittal, Institute of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, LEARN! - Brain, learning and development, EMGO+ - Mental Health, LEARN!, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, State University of New York (SUNY)-State University of New York (SUNY), Department of Neuroscience and Physiology, Faculty of Land and Environment, Biosciences Research Division, Department of Environment and Primary Industries Victoria, Department of Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), University of California-University of California, Universität Heidelberg [Heidelberg], Cornell University [New York]-Weill Medical College of Cornell University [New York], Bioinformatics, Internal Medicine, Portland Va Medical Center : Ganzini Linda MD, Technische Universität Dresden = Dresden University of Technology (TU Dresden)-University Hospital Carl Gustav Carus, Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of California [Irvine] (UCI), University of California-University of California-University of California [Los Angeles] (UCLA), University of Bonn, University of California-University of California-David Geffen School of Medicine [Los Angeles], Cardiff University-Medical Research Council, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Göttingen - Georg-August-Universität Göttingen, Yale University School of Medicine, Georg-August-University [Göttingen], ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK, Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O'Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR, Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A, Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ, Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF, Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ, O'Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR, Cardiff University-Medical Research Council (MRC), HudsonAlpha Institute for Biotechnology, The Institute of Psychiatry-King‘s College London, Cornell University-Weill Medical College of Cornell University [New York], Stanford University Medical School, Technische Universität Dresden (TUD)-University Hospital Carl Gustav Carus, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, McGill University-Montreal Children's Hospital, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Stanford University School of Medicine [Stanford], Stanford University [Stanford], Eberhard Karls Universität Tübingen, Friedrich Alexander University [Erlangen-Nürnberg], Università di Bologna [Bologna] (UNIBO), University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Washington University School of Medicine, Ghent University [Belgium] (UGENT), University of Goettingen, CHUM Research Center, Psychiatry and Behavioral Science, Stanford University School of Medicine [CA, USA], Aalborg Psychiatric Hospital, Aarhus University Hospital, Washington University in St Louis, Instituto Nacional de Saude Dr Ricardo Jorge, Oades, Robert D., Guellaen, Georges, Medical Oncology, Epidemiology, Child and Adolescent Psychiatry / Psychology, and Hematology
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Netherlands Twin Register (NTR) ,Medizin ,Inheritance Patterns ,Social Sciences ,AUTISM SPECTRUM DISORDERS ,nosology ,heritability ,COMMON SNPS ,0302 clinical medicine ,Crohn Disease ,SCHIZOPHRENIA ,Child ,Psychiatric genetics ,Genetics & Heredity ,MAJOR DEPRESSIVE DISORDER ,RISK ,0303 health sciences ,ATTENTION-DEFICIT/HYPERACTIVITY DISORDER ,120 000 Neuronal Coherence ,Mental Disorders ,Variants ,BIPOLAR DISORDER ,ASSOCIATION ,Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3] ,Psychiatric Disorders ,CROHNS-DISEASE ,3. Good health ,Schizophrenia ,genetic association study ,Medical genetics ,Major depressive disorder ,SNPs ,Adult ,medicine.medical_specialty ,genetic etiology ,medical genetics ,DEFICIT HYPERACTIVITY DISORDER ,Biology ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Article ,Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3] ,Heritability ,Genetic Heterogeneity ,03 medical and health sciences ,Prevalence of mental disorders ,mental disorders ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Genetics ,medicine ,ddc:61 ,Humans ,Attention deficit hyperactivity disorder ,Genetic Predisposition to Disease ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,DCN PAC - Perception action and control NCEBP 9 - Mental health ,ddc:610 ,Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters ,Bipolar disorder ,Psychiatry ,030304 developmental biology ,Depressive Disorder, Major ,Genome, Human ,Genetic heterogeneity ,medicine.disease ,schizophrenia ,Attention Deficit Disorder with Hyperactivity ,Child Development Disorders, Pervasive ,Perturbações do Desenvolvimento Infantil e Saúde Mental ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
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- 2013
19. A high-resolution anatomical atlas of the transcriptome in the mouse embryo
- Author
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Graciana Diez-Roux, Sandro Banfi, Marc Sultan, Lars Geffers, Santosh Anand, David Rozado, Alon Magen, Elena Canidio, Massimiliano Pagani, Ivana Peluso, Nathalie Lin-Marq, Muriel Koch, Marchesa Bilio, Immacolata Cantiello, Roberta Verde, Cristian De Masi, Salvatore A Bianchi, Juliette Cicchini, Elodie Perroud, Shprese Mehmeti, Emilie Dagand, Sabine Schrinner, Asja Nürnberger, Katja Schmidt, Katja Metz, Christina Zwingmann, Norbert Brieske, Cindy Springer, Ana Martinez Hernandez, Sarah Herzog, Frauke Grabbe, Cornelia Sieverding, Barbara Fischer, Kathrin Schrader, Maren Brockmeyer, Sarah Dettmer, Christin Helbig, Violaine Alunni, Marie-Annick Battaini, Carole Mura, Charlotte N Henrichsen, Raquel Garcia-Lopez, Diego Echevarria, Eduardo Puelles, Elena Garcia-Calero, Stefan Kruse, Markus Uhr, Christine Kauck, Guangjie Feng, Nestor Milyaev, Chuang Kee Ong, Lalit Kumar, MeiSze Lam, Colin A Semple, Attila Gyenesei, Stefan Mundlos, Uwe Radelof, Hans Lehrach, Paolo Sarmientos, Alexandre Reymond, Duncan R Davidson, Pascal Dollé, Stylianos E Antonarakis, Marie-Laure Yaspo, Salvador Martinez, Richard A Baldock, Gregor Eichele, Andrea Ballabio, Telethon Institute for Genetics and Medicine, Telethon Institute, Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Genes and Behavior Department [Göttingen], Max Planck Institute for Biophysical Chemistry (MPI-BPC), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Primm, Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Experimental Embryology Lab, Universidad Miguel Hernández [Elche] (UMH)-Instituto de Neurociencias, ORGARAT, Human Genetics Unit, Medical Research Council, Deutsches Ressourcenzentrum für Genomforschung (RZPD), Deutsches Ressourcenzentrum für Genomforschung, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Medical Genetics, Università degli studi di Napoli Federico II, Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital [Houston, USA], This work was supported by the EC VI Framework Programme contract number LSHG-CT-2004-512003. The authors also acknowledge the support of: the Italian Telethon Foundation (AB, SB, and GD-R), the Swiss National Science Foundation (AR and SEA), the Max Planck Society (GE, M-LY, HL), MRC (RB, DD), Association pour la Recherche sur le Cancer (PD), and Ingenio 2010 MEC-CONSOLIDER CSD2007-00023, DIGESIC-MEC BFU2008-00588, CIBERSAM/ISCIII (SM)., Université de Genève = University of Geneva (UNIGE), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), University of Naples Federico II = Università degli studi di Napoli Federico II, Autard, Delphine, Diez Roux, G, Banfi, Sandro, Sultan, M, Geffers, L, Anand, S, Rozado, D, Magen, A, Canidio, E, Pagani, M, Peluso, I, Lin Marq, N, Koch, M, Bilio, M, Cantiello, I, Verde, R, De Masi, C, Bianchi, Sa, Cicchini, J, Perroud, E, Mehmeti, S, Dagand, E, Schrinner, S, Nürnberger, A, Schmidt, K, Metz, K, Zwingmann, C, Brieske, N, Springer, C, Martinez Hernandez, A, Herzog, S, Grabbe, F, Sieverding, C, Fischer, B, Schrader, K, Bürsing, M, Schubert, S, Helbig, C, Alunni, V, Battaini, Ma, Mura, C, Henrichsen, Cn, Garcia Lopez, R, Echevarria, D, Puelles, E, Garcia Calero, E, Kruse, S, Uhr, M, Kauck, C, Feng, G, Milyaev, N, Ong, Ck, Kumar, L, Lam, M, Semple, Ca, Gyenesei, A, Mundlos, S, Radelof, U, Lehrach, H, Sarmientos, P, Reymond, A, Davidson, Dr, Dollé, P, Antonarakis, Se, Yaspo, Ml, Martinez, M, Baldock, Ra, Eichele, G, Ballabio, A., Banfi, S, Reymond, R, Martinez, S, Ballabio, Andrea, and Reymond, Alexandre
- Subjects
Transcriptome ,Mice ,0302 clinical medicine ,Databases, Genetic ,Gene expression ,Animals ,Atlases as Topic ,Embryo, Mammalian ,Gene Expression Profiling ,Internet ,Mice/anatomy & histology ,Mice/embryology ,Mice, Inbred C57BL ,Organ Specificity ,ddc:576.5 ,MESH: Animals ,Biology (General) ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,MESH: Databases, Genetic ,MESH: Organ Specificity ,Genetics ,0303 health sciences ,Agricultural and Biological Sciences(all) ,General Neuroscience ,Wnt signaling pathway ,Genetics and Genomics/Gene Expression ,Genome project ,MESH: Internet ,General Agricultural and Biological Sciences ,Research Article ,Genetics and Genomics/Animal Genetics ,QH301-705.5 ,Neuroscience(all) ,education ,MESH: Atlases as Topic ,In situ hybridization ,Computational biology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,MESH: Gene Expression Profiling ,Mice/anatomy & histology/embryology/genetics ,MESH: Mice, Inbred C57BL ,Immunology and Microbiology(all) ,microRNA ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,Gene ,MESH: Mice ,030304 developmental biology ,General Immunology and Microbiology ,Biochemistry, Genetics and Molecular Biology(all) ,MESH: Embryo, Mammalian ,Gene expression profiling ,Genetics and Genomics/Genome Projects ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The manuscript describes the “digital transcriptome atlas” of the developing mouse embryo, a powerful resource to determine co-expression of genes, to identify cell populations and lineages and to identify functional associations between genes relevant to development and disease., Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease., Author Summary In situ hybridization (ISH) can be used to visualize gene expression in cells and tissues in their native context. High-throughput ISH using nonradioactive RNA probes allowed the Eurexpress consortium to generate a comprehensive, interactive, and freely accessible digital gene expression atlas, the Eurexpress transcriptome atlas (http://www.eurexpress.org), of the E14.5 mouse embryo. Expression data for over 15,000 genes were annotated for hundreds of anatomical structures, thus allowing us to systematically identify tissue-specific and tissue-overlapping gene networks. We illustrate the value of the Eurexpress atlas by finding novel regional subdivisions in the developing brain. We also use the transcriptome atlas to allocate specific components of the complex Wnt signaling pathway to kidney development, and we identify regionally expressed genes in liver that may be markers of hematopoietic stem cell differentiation.
- Published
- 2011
- Full Text
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