Discovery and Validation of Novel Genes in a Large Chinese Autism Spectrum Disorder Cohort

doi:10.1016/j.biopsych.2023.06.025

科研成果详情

题名	Discovery and Validation of Novel Genes in a Large Chinese Autism Spectrum Disorder Cohort
作者	Wang, Jincheng 1,2; Yu, Juehua 1; Wang, Mengdi 3; Zhang, Lingli 1; Yang, Kan 1; Du, Xiujuan 1; Wu, Jinyu 4; Wang, Xiaoqun 3,5; Li, Fei 1; Qiu, Zilong 1,2,6,7,8
发表日期	2023-11-15
发表期刊	BIOLOGICAL PSYCHIATRY 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Autism spectrum disorder High-functioning autism Mouse models Single-cell sequencing Social behaviors Whole-exome sequencing
其他关键词	MUTATIONS ; INSIGHTS ; SERVER
摘要	BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that causes impairments in social communication and stereotypical behaviors, often accompanied by developmental delay or intellectual disability. A growing body of evidence suggests that ASD is highly heritable, and genetic studies have defined numerous risk genes. However, most studies have been conducted with individuals of European and Hispanic ancestry, and there is a lack of genetic analyses of ASD in the East Asian population. METHODS: We performed whole-exome sequencing on 772 Chinese ASD trios and combined the data with a previous study of 369 Chinese ASD trios, identifying de novo variants in 1141 ASD trios. We used single-cell RNA sequencing analysis to identify the cell types in which ASD-related genes were enriched. In addition, we validated the function of a candidate high-functioning autism gene in mouse models using genetic approaches. RESULTS: Our findings showed that ASD without developmental delay or intellectual disability carried fewer disruptive de novo variants than ASD with developmental delay or intellectual disability. Moreover, we identified 9 novel ASD candidate genes that were not present in the current ASD gene database. We further validated one such novel ASD candidate gene, SLC35G1, by showing that mice harboring a heterozygous deletion of Slc35g1 exhibited defects in interactive social behaviors. CONCLUSIONS: Our work nominates novel ASD candidate genes and emphasizes the importance of genome-wide genetic studies with ASD cohorts of different ancestries to reveal the comprehensive genetic architecture of ASD.
资助项目	Zhejiang Jiaxing Charity Foundation; National Natural Science Foundation of China [32000726, 82125032, 81930095, 82001211, 81761128035, 82021001]; MOST [2019YFA0110100, 2017YFA010330]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB32060202]; Program of Shanghai Academic Research Leader; Science and Technology Commission of Shanghai Municipality [2018SHZDZX05, 19410713500, 2018SHZDZX01]; Shanghai Municipal Commission of Health and Family Planning [GWV-10.1-XK07, 2020CXJQ01, 2018YJRC03, 2018BR33]; Guangdong Key Project [2018B030335001]; China Postdoctoral Science Foundation-Chinese Academy of Sciences Joint Foundation for Excellent Postdoctoral Fellows [2017LH036]; China Postdoctoral Science Foundation [2017M620173]; Guang Ci Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine
出版者	ELSEVIER SCIENCE INC
ISSN	0006-3223
EISSN	1873-2402
卷号	94 期号:10 页码:792-803
DOI	10.1016/j.biopsych.2023.06.025
页数	12
WOS类目	Neurosciences ; Psychiatry
WOS研究方向	Neurosciences & Neurology ; Psychiatry
WOS记录号	WOS:001155229900001
收录类别	SCIE ; SCOPUS
在线发表日期	2023-10
URL	查看原文
PubMed ID	37393044
SCOPUSEID	2-s2.0-85168595102
通讯作者地址	[Li, Fei]Department of Developmental and Behavioural Pediatric & Child Primary Care,Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research,Institute of Autism,and MOE-Shanghai Key Laboratory for Children's Environmental Health,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China
Scopus学科分类	Biological Psychiatry
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/206854
专题	基因组医学研究院
通讯作者	Li, Fei; Qiu, Zilong
作者单位	1.Department of Developmental and Behavioural Pediatric & Child Primary Care,Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research,Institute of Autism,and MOE-Shanghai Key Laboratory for Children's Environmental Health,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 2.Institute of Neuroscience,State Key Laboratory of Neuroscience,CAS Center for Excellence in Brain Science and Intelligence Technology,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai,China; 3.Institute of Biophysics,Chinese Academy of Sciences,Beijing,China; 4.Institute of Genomic Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,China; 5.State Key Laboratory of Cognitive Neuroscience and Learning,IDG/McGovern Institute for Brain Research,Beijing Normal University,Beijing,China; 6.Songjiang Research Institute,Songjiang District Central Hospital,and Institute of Autism,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 7.Clinical Neuroscience Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 8.National Clinical Research Center for Aging and Medicine,Huashan Hospital,Fudan University,Shanghai,China
推荐引用方式 GB/T 7714	Wang, Jincheng,Yu, Juehua,Wang, Mengdi,et al. Discovery and Validation of Novel Genes in a Large Chinese Autism Spectrum Disorder Cohort[J]. BIOLOGICAL PSYCHIATRY,2023,94(10):792-803.
APA	Wang, Jincheng., Yu, Juehua., Wang, Mengdi., Zhang, Lingli., Yang, Kan., ... & Qiu, Zilong. (2023). Discovery and Validation of Novel Genes in a Large Chinese Autism Spectrum Disorder Cohort. BIOLOGICAL PSYCHIATRY, 94(10), 792-803.
MLA	Wang, Jincheng,et al."Discovery and Validation of Novel Genes in a Large Chinese Autism Spectrum Disorder Cohort".BIOLOGICAL PSYCHIATRY 94.10(2023):792-803.