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Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study
L. Hou, U. Heilbronner, F. Degenhardt, M. Adli, K. Akiyama, N. Akula, R. Ardau, B. Arias, L. Backlund, CE. Banzato, A. Benabarre, S. Bengesser, AK. Bhattacharjee, JM. Biernacka, A. Birner, C. Brichant-Petitjean, ET. Bui, P. Cervantes, GB. Chen,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu klinické zkoušky, časopisecké články, multicentrická studie, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, práce podpořená grantem
Grantová podpora
NT13891
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
Zdroj
NLK
ProQuest Central
od 1992-01-04 do Před 3 měsíci
Nursing & Allied Health Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Health & Medicine (ProQuest)
od 1992-01-04 do Před 3 měsíci
Family Health Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Psychology Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Health Management Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
Public Health Database (ProQuest)
od 1992-01-04 do Před 3 měsíci
- MeSH
- bipolární porucha farmakoterapie genetika MeSH
- celogenomová asociační studie MeSH
- fenotyp MeSH
- genetická variace MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- receptory GDNF genetika MeSH
- sloučeniny lithia terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.
Bipolar Center Wiener Neustadt Wiener Neustadt Austria
Campus for Ageing and Vitality Newcastle University Newcastle upon Tyne UK
Child and Adolescent Psychiatry Research Center Stockholm Sweden
Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland
Department of Biomedical Sciences University of Cagliari Cagliari Italy
Department of Biomedicine Aarhus University Aarhus Denmark
Department of Clinical Neurosciences Karolinska Institutet Stockholm Sweden
Department of Health Sciences Research Mayo Clinic Rochester MN USA
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Pharmacology Dalhousie University Halifax NS Canada
Department of Pharmacy VA San Diego Healthcare System San Diego CA USA
Department of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore MD USA
Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA
Department of Psychiatry and Psychotherapy Ludwig Maximilians University Munich Munich Germany
Department of Psychiatry Dalhousie University Halifax Nova Scotia NS Canada
Department of Psychiatry Dokkyo Medical University School of Medicine Mibu Japan
Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo Japan
Department of Psychiatry Lindner Center of Hope University of Cincinnati Mason OH USA
Department of Psychiatry Massachusetts General Hospital and Harvard Medical School Boston MA USA
Department of Psychiatry Nagoya University Graduate School of Medicine Nagoya Japan
Department of Psychiatry University of Antioquia Medellín Medellín Colombia
Department of Psychiatry University of Calgary Calgary AB Canada
Department of Psychiatry University of California San Diego San Diego CA USA
Department of Psychiatry University of Campinas Campinas Brazil
Department of Psychiatry University of Iowa Iowa City IA USA
Department of Psychiatry University of Naples SUN Naples Italy
Department of Psychiatry University of Toronto Toronto ON Canada
Department of Psychiatry VA San Diego Healthcare System San Diego CA USA
Discipline of Psychiatry University of Adelaide Adelaide SA Australia
Douglas Mental Health University Institute McGill University Montreal QC Canada
Fliedner Klinik Berlin Center for Psychiatry Psychotherapy and Psychosomatic Medicine Berlin Germany
Human Genomics Research Group Department of Biomedicine University Hospital Basel Basel Switzerland
Inserm U955 Psychiatrie Translationnelle Créteil France
Institute of Epidemiology and Preventive Medicine National Taiwan University Taipei Taiwan
Institute of Psychiatric Phenomics and Genomics Ludwig Maximilians University Munich Munich Germany
Laboratory for Molecular Dynamics of Mental Disorders RIKEN Brain Science Institute Saitama Japan
Mental Illness Research Theme Neuroscience Research Australia Sydney NSW Australia
Montreal Neurological Institute and Hospital McGill University Montreal QC Canada
Mood Disorders Center of Ottawa Ottawa ON Canada
National Institute of Mental Health Klecany Czech Republic
Neurosciences Section Department of Medicine and Surgery University of Salerno Salerno Italy
Pôle de Psychiatrie Générale Universitaire Centre Hospitalier Charles Perrens Bordeaux France
Psychiatric Genetic Unit Poznan University of Medical Sciences Poznan Poland
School of Medical Sciences University of New South Wales Sydney NSW Australia
School of Psychiatry University of New South Wales and Black Dog Institute Sydney NSW Australia
The Neuromodulation Unit McGill University Health Centre Montreal QC Canada
The University of Queensland Queensland Brain Institute Brisbane Queensland QLD Australia
Unit of Clinical Pharmacology Hospital University Agency of Cagliari Cagliari Italy
Veterans Administration San Diego Healthcare System San Diego CA USA
Citace poskytuje Crossref.org
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- $a Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study / $c L. Hou, U. Heilbronner, F. Degenhardt, M. Adli, K. Akiyama, N. Akula, R. Ardau, B. Arias, L. Backlund, CE. Banzato, A. Benabarre, S. Bengesser, AK. Bhattacharjee, JM. Biernacka, A. Birner, C. Brichant-Petitjean, ET. Bui, P. Cervantes, GB. Chen, HC. Chen, C. Chillotti, S. Cichon, SR. Clark, F. Colom, DA. Cousins, C. Cruceanu, PM. Czerski, CR. Dantas, A. Dayer, B. Étain, P. Falkai, AJ. Forstner, L. Frisén, JM. Fullerton, S. Gard, JS. Garnham, FS. Goes, P. Grof, O. Gruber, R. Hashimoto, J. Hauser, S. Herms, P. Hoffmann, A. Hofmann, S. Jamain, E. Jiménez, JP. Kahn, L. Kassem, S. Kittel-Schneider, S. Kliwicki, B. König, I. Kusumi, N. Lackner, G. Laje, M. Landén, C. Lavebratt, M. Leboyer, SG. Leckband, CA. Jaramillo, G. MacQueen, M. Manchia, L. Martinsson, M. Mattheisen, MJ. McCarthy, SL. McElroy, M. Mitjans, FM. Mondimore, P. Monteleone, CM. Nievergelt, MM. Nöthen, U. Ösby, N. Ozaki, RH. Perlis, A. Pfennig, D. Reich-Erkelenz, GA. Rouleau, PR. Schofield, KO. Schubert, BW. Schweizer, F. Seemüller, G. Severino, T. Shekhtman, PD. Shilling, K. Shimoda, C. Simhandl, CM. Slaney, JW. Smoller, A. Squassina, T. Stamm, P. Stopkova, SK. Tighe, A. Tortorella, G. Turecki, J. Volkert, S. Witt, A. Wright, LT. Young, PP. Zandi, JB. Potash, JR. DePaulo, M. Bauer, EZ. Reininghaus, T. Novák, JM. Aubry, M. Maj, BT. Baune, PB. Mitchell, E. Vieta, MA. Frye, JK. Rybakowski, PH. Kuo, T. Kato, M. Grigoroiu-Serbanescu, A. Reif, M. Del Zompo, F. Bellivier, M. Schalling, NR. Wray, JR. Kelsoe, M. Alda, M. Rietschel, FJ. McMahon, TG. Schulze,
- 520 9_
- $a BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Arias, Bárbara $u Department of Biologia Animal, Unitat d'Antropologia (Dp Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Catalonia, Spain. $7 gn_A_00008410
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Chillotti, Caterina $u Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
- 700 1_
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- 700 1_
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- 700 1_
- $a Colom, Francesc $u Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
- 700 1_
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- 700 1_
- $a Cruceanu, Cristiana $u Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Frisén, Louise $u Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Smoller, Jordan W $u Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- 700 1_
- $a Squassina, Alessio $u Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
- 700 1_
- $a Stamm, Thomas $u Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
- 700 1_
- $a Stopkova, Pavla $u National Institute of Mental Health, Klecany, Czech Republic.
- 700 1_
- $a Tighe, Sarah K $u Department of Psychiatry, University of Iowa, Iowa City, IA, USA; University of Iowa Carver College of Medicine and University of Iowa College of Public Health, VA Quality Scholars Program, Iowa City VA Hospital, Iowa City, IA, USA.
- 700 1_
- $a Tortorella, Alfonso $u Department of Psychiatry, University of Naples SUN, Naples, Italy.
- 700 1_
- $a Turecki, Gustavo $u Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
- 700 1_
- $a Volkert, Julia $u Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
- 700 1_
- $a Witt, Stephanie $u Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- 700 1_
- $a Wright, Adam $u School of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, NSW, Australia.
- 700 1_
- $a Young, L Trevor $u Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
- 700 1_
- $a Zandi, Peter P $u Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
- 700 1_
- $a Potash, James B $u Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
- 700 1_
- $a DePaulo, J Raymond $u Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
- 700 1_
- $a Bauer, Michael $u Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
- 700 1_
- $a Reininghaus, Eva Z $u Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Department of Psychiatry, Medical University of Graz, Graz, Austria.
- 700 1_
- $a Novák, Tomas $u National Institute of Mental Health, Klecany, Czech Republic.
- 700 1_
- $a Aubry, Jean-Michel $u Department of Mental Health and Psychiatry, Mood Disorders Unit-Geneva University Hospitals, Geneva, Switzerland.
- 700 1_
- $a Maj, Mario $u Department of Psychiatry, University of Naples SUN, Naples, Italy.
- 700 1_
- $a Baune, Bernhard T $u Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
- 700 1_
- $a Mitchell, Philip B $u School of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, NSW, Australia.
- 700 1_
- $a Vieta, Eduard $u Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
- 700 1_
- $a Frye, Mark A $u Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
- 700 1_
- $a Rybakowski, Janusz K $u Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
- 700 1_
- $a Kuo, Po-Hsiu $u Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
- 700 1_
- $a Kato, Tadafumi $u Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
- 700 1_
- $a Grigoroiu-Serbanescu, Maria $u Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Psychiatric Hospital, Bucharest, Romania.
- 700 1_
- $a Reif, Andreas $u Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
- 700 1_
- $a Del Zompo, Maria $u Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
- 700 1_
- $a Bellivier, Frank $u INSERM UMR-S 1144-Université Paris Diderot Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F Widal, Paris, France.
- 700 1_
- $a Schalling, Martin $u Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
- 700 1_
- $a Wray, Naomi R $u The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, QLD, Australia.
- 700 1_
- $a Kelsoe, John R $u Veterans Administration, San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
- 700 1_
- $a Alda, Martin $u Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, NS, Canada; National Institute of Mental Health, Klecany, Czech Republic.
- 700 1_
- $a Rietschel, Marcella $u Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- 700 1_
- $a McMahon, Francis J $u Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA. Electronic address: mcmahonf@mail.nih.gov.
- 700 1_
- $a Schulze, Thomas G $u Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA; Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: thomas.schulze@med.uni-muenchen.de.
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