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

IMR OpenIR

	Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia
	Tang Jinsong 1; Fan Yu 4; Li Hong 1; Xiang Qun 4; Zhang DengFeng 4; Li Zongchang 1; He Ying 1; Liao Yanhui 1; Wang Ya 7; He Fan 8; Zhang Fengyu 1; Shugart Yin Yao 11; Liu Chunyu 12; Tang Yanqing 13; Chan Raymond C K 7; Wang ChuanYue 8; Yao YongGang 4; Chen Xiaogang 1
	2017
发表期刊	JOURNAL OF GENETICS AND GENOMICS
ISSN	1673-8527
卷号	44 期号:6 页码:295-306
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 non-synonymous 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. Copyright (C) 2017, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.
其他摘要	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 non-synonymous 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.
关键词	DE-NOVO MUTATIONS STRUCTURAL VARIANT DISCOVERY WIDE ASSOCIATION PSYCHIATRIC-DISORDERS SYNAPTIC PLASTICITY BIPOLAR DISORDER PROTEIN FUNCTION COMPLEX TRAITS MESSENGER-RNA HUMAN-DISEASE Whole-genome sequencing Schizophrenia Monozygotic twin De novo mutation Combined effect Susceptibility
收录类别	CSCD
语种	英语
资助项目	[Strategic Priority Research Program of the Chinese Academy of Sciences] ; [Bureau of Frontier Sciences and Education, Chinese Academy of Sciences] ; [National Natural Science Foundation of China] ; [Beijing Training Project for the Leading Talents in S T] ; [National Key Basic Research and Development Program (973)] ; [CAS/SAFEA International Partnership Programme for Creative Research Teams]
CSCD记录号	CSCD:6023344
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/155109
专题	中国科学院金属研究所
作者单位	1.中国科学院大气物理研究所 2.Cent S Univ, Xiangya Hosp 2, Natl Technol Institute Psychiat, Changsha 410011, Hunan, Peoples R China 3.Cent S University, Xiangya Hosp 2, Key Lab Psychiat & Mental Hlth Hunan Prov, Changsha 410011, Hunan, Peoples R China 4.中国科学院昆明动物研究所 5.郑州大学 6.中国科学院大学 7.中国科学院 8.Capital Med University, Beijing Key Lab Mental Disorders, Dept Psychiat, Beijing Anding Hosp, Beijing 100088, Peoples R China 9.Capital Med Univ, Ctr Schizophrenia, Beijing Institute Brain Disorders, Minist Sci & Technol, Beijing 100088, Peoples R China 10.Capital Med University, Lab Brain Disorders, Minist Sci & Technol, Beijing 100088, Peoples R China 11.NIMH, Unit Stat Genom, Intramural Res Programs, NIH, Bethesda, MD 20892 USA 12.Univ Illinois, Institute Human Genet, Chicago, IL 60607 USA 13.中国科学院金属研究所 14.Chinese Acad Science, CAS Ctr Excellence Brain Science & Intelligence Techn, Shanghai 200031, Peoples R China CAS Ctr Excellence Brain Science & Intelligence Techn
推荐引用方式 GB/T 7714	Tang Jinsong,Fan Yu,Li Hong,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(6):295-306.
APA	Tang Jinsong.,Fan Yu.,Li Hong.,Xiang Qun.,Zhang DengFeng.,...&Chen Xiaogang.(2017).Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia.JOURNAL OF GENETICS AND GENOMICS,44(6),295-306.
MLA	Tang Jinsong,et al."Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia".JOURNAL OF GENETICS AND GENOMICS 44.6(2017):295-306.