The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 转化基因组

	The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
	Chang H 1; Hoshina N 2,3; Wu DD 7; Schulze TG 19; Rietschel M 17; Li M[*]1; Zhang C 4; Ma Y 5; Cao H 6
刊名	Molecular Psychiatry
	2017
卷号	期号:页码:publication online
通讯作者	tadashi.yamamoto@oist.jp or marcella.rietschel@zi-mannheim.de or limingkiz@mail.kiz.ac.cn
英文摘要	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.
资助信息	This work was also supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A to SC and MMN, grant 01ZX1314G to MR). MMN is a member of the DFG-funded Excellence-Cluster ImmunoSensation. The study was also supported funded by UEFISCDI, Bucharest, Romania, grant no. 89/2012 to MGS and by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (grant 01ZX1314A to MMN and SC). Funding for the Swedish collection was provided by the Stanley Center for Psychiatric Research, Broad Institute from a grant from Stanley Medical Research Institute. We thank the Okinawa Institute of Science and Technology Graduate University for generous support to TY and NH. We also wish to thank the BBMRI.se and KI Biobank at Karolinska Institutet for professional biobank service. We are grateful to Sue O’Shea Ph.D., and Melvin McInnis MD, of the University of Michigan for providing detailed expression data on PCDH17, which was generated with the support of the Steven Schwartzberg Memorial Fund and Prechter Bipolar Research Fund. The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme ‘Quality of Life and Management of the Living Resources’ of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from The Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing was supported by the ZonMw grant (project 91111025).by the German Research Foundation (DFG; grant FOR2107, RI908/11-1 to MR, NO246/10-1 to MMN). The Romanian sample recruitment and genotyping was
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10801]
专题	昆明动物研究所_转化基因组昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_遗传资源与进化国家重点实验室昆明动物研究所_进化与发育转录组学
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, Chin 2.Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan 3.Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA 4.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, Chin 5.State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China; 6.Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 7.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 8.Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 9.Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA 10.Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
推荐引用方式 GB/T 7714	Chang H,Hoshina N,Wu DD,et al. The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders[J]. Molecular Psychiatry,2017,():publication online.
APA	Chang H.,Hoshina N.,Wu DD.,Schulze TG.,Rietschel M.,...&Cao H.(2017).The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders.Molecular Psychiatry,(),publication online.
MLA	Chang H,et al."The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders".Molecular Psychiatry .(2017):publication online.