Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

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	Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia
	Xiang Q 2,3; Zhang DF 3; yanqingtang@163.com ; rckchan@psych.ac.cn ; Cwang.cy@163.net ; yaoyg@mail.kiz.ac.cn ; chenxghn@163. com ; Liu CY 8; He Y 4; Li ZC 4
刊名	Journal of Genetics and Genomics
	2017
卷号	44 期号:X 页码:295-306
关键词	Whole-genome Sequencing Schizophrenia Monozygotic Twi De Novo Mutatio Combined Effec Susceptibility
英文摘要	Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight nonsynonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.
语种	英语
资助机构	This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 and XDB02030002), the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005) and the Na- tional Natural Science Foundation of China (Nos. 81088001, 81271484, 81471361 and 81371480), the Beijing Training Project for the Leading Talents in S & T (Z151100000315020), the National Key Basic Research and Development Program (973) (2012CB517904), the CAS/SAFEA International Partnership Programme for Creative Research Teams (Y2CX131003). ; This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 and XDB02030002), the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005) and the Na- tional Natural Science Foundation of China (Nos. 81088001, 81271484, 81471361 and 81371480), the Beijing Training Project for the Leading Talents in S & T (Z151100000315020), the National Key Basic Research and Development Program (973) (2012CB517904), the CAS/SAFEA International Partnership Programme for Creative Research Teams (Y2CX131003). ; This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 and XDB02030002), the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005) and the Na- tional Natural Science Foundation of China (Nos. 81088001, 81271484, 81471361 and 81371480), the Beijing Training Project for the Leading Talents in S & T (Z151100000315020), the National Key Basic Research and Development Program (973) (2012CB517904), the CAS/SAFEA International Partnership Programme for Creative Research Teams (Y2CX131003). ; This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 and XDB02030002), the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005) and the Na- tional Natural Science Foundation of China (Nos. 81088001, 81271484, 81471361 and 81371480), the Beijing Training Project for the Leading Talents in S & T (Z151100000315020), the National Key Basic Research and Development Program (973) (2012CB517904), the CAS/SAFEA International Partnership Programme for Creative Research Teams (Y2CX131003).
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/11761]
专题	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_重大疾病机理的遗传学
通讯作者	yanqingtang@163.com; rckchan@psych.ac.cn; Cwang.cy@163.net; yaoyg@mail.kiz.ac.cn; chenxghn@163. com
作者单位	1.Neuropsychology and Applied Cognitive Neuroscience Laboratory, and CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China 3.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China 4.Institute of Mental Health, National Clinical Research Center for Mental Health Disorders and National Technology Institute of Psychiatry, and Key Laboratory of Psychiatry and Mental Health of Hunan Province, The Second Xiangya Hospital, Central South University, Changsha 410011, China 5.Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China 6.CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 7.Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang 110122, China 8.Institute of Human Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA 9.Unit on Statistical Genomics, Intramural Research Programs, National Institute of Mental Health, NIH, Bethesda 20892, USA 10.Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, and Center of Schizophrenia, Beijing Institute for Brain Disorders and Laboratory of Brain Disorders of the Ministry of Science and Technology, Capital Medical University, Beijing 100088, China
推荐引用方式 GB/T 7714	Xiang Q,Zhang DF,yanqingtang@163.com,et al. Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia[J]. Journal of Genetics and Genomics,2017,44(X):295-306.
APA	Xiang Q.,Zhang DF.,yanqingtang@163.com.,rckchan@psych.ac.cn.,Cwang.cy@163.net.,...&Chen XG*.(2017).Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia.Journal of Genetics and Genomics,44(X),295-306.
MLA	Xiang Q,et al."Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia".Journal of Genetics and Genomics 44.X(2017):295-306.