Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
28070120
TITLE
The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders.
ABSTRACT
NlmCategory: UNASSIGNED
Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.Molecular Psychiatry advance online publication, 10 January 2017; doi:10.1038/mp.2016.231.
DATE PUBLISHED
2017 Jan 10
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/06/07
revised 2016/10/27
accepted 2016/11/01
entrez 2017/01/11 06:00
pubmed 2017/01/11 06:00
medline 2017/01/11 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Chang H Chang H H Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Hoshina N Hoshina N N Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Zhang C Zhang C C Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ma Y Ma Y Y State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
Cao H Cao H H Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Wang Y Wang Y Y State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Wu DD Wu D-D DD State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Bergen SE Bergen S E SE Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Landén M Landén M M Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
Hultman CM Hultman C M CM Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Preisig M Preisig M M Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.
Kutalik Z Kutalik Z Z Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Castelao E Castelao E E Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.
Grigoroiu-Serbanescu M Grigoroiu-Serbanescu M M Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
Forstner AJ Forstner A J AJ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Strohmaier J Strohmaier J J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Hecker J Hecker J J Institute of Genomic Mathematics, University of Bonn, Bonn, Germany.
Schulze TG Schulze T G TG Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.
Müller-Myhsok B Müller-Myhsok B B University of Liverpool, Institute of Translational Medicine, Liverpool, UK.
Reif A Reif A A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Mitchell PB Mitchell P B PB Black Dog Institute, Sydney, NSW, Australia.
Martin NG Martin N G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Schofield PR Schofield P R PR School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Cichon S Cichon S S Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Centre Jülich, Jülich, Germany.
Nöthen MM Nöthen M M MM Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Swedish Bipolar Study Group
MooDS Bipolar Consortium
Walter H Walter H H Department of Psychiatry and Psychotherapy, Universitätsmedizin Charité, Berlin, Germany.
Erk S Erk S S Department of Psychiatry and Psychotherapy, Universitätsmedizin Charité, Berlin, Germany.
Heinz A Heinz A A Department of Psychiatry and Psychotherapy, Universitätsmedizin Charité, Berlin, Germany.
Amin N Amin N N Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
van Duijn CM van Duijn C M CM Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Meyer-Lindenberg A Meyer-Lindenberg A A Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Tost H Tost H H Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Xiao X Xiao X X Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Yamamoto T Yamamoto T T Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.
Rietschel M Rietschel M M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Li M Li M M Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Backlund Lena L
Frisén Louise L
Lavebratt Catharina C
Schalling Martin M
Ösby Urban U
Mühleisen Thomas W TW
Leber Markus M
Degenhardt Franziska F
Treutlein Jens J
Mattheisen Manuel M
Maaser Anna A
Meier Sandra S
Herms Stefan S
Hoffmann Per P
Lacour André A
Witt Stephanie H SH
Streit Fabian F
Lucae Susanne S
Maier Wolfgang W
Schwarz Markus M
Vedder Helmut H
Kammerer-Ciernioch Jutta J
Pfennig Andrea A
Bauer Michael M
Hautzinger Martin M
Wright Adam A
Fullerton Janice M JM
Montgomery Grant W GW
Medland Sarah E SE
Gordon Scott D SD
Becker Tim T
Schumacher Johannes J
Propping Peter P
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2017
MONTH: Jan
DAY: 10
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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