title: Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort.
abstract: Autism spectrum disorder (ASD) describes a group of neurodevelopmental disorders with high heritability, although the underlying genetic determinants of ASDs remain largely unknown. Large-scale whole-genome studies of copy number variation in Han Chinese samples are still lacking. We performed a genome-wide copy number variation analysis of 343 ASD trios, 203 patients with sporadic cases and 988 controls in a Chinese population using Illumina genotyping platforms to identify CNVs and related genes that may contribute to ASD risk. We identified 32 rare CNVs larger than 1 Mb in 31 patients. ASD patients were found to carry a higher global burden of rare, large CNVs than controls. Recurrent de novo or case-private CNVs were found at 15q11-13, Xp22.3, 15q13.1-13.2, 3p26.3 and 2p12. The de novo 15q11-13 duplication was more prevalent in this Chinese population than in those with European ancestry. Several genes, including GRAMD2 and STAM, were implicated as novel ASD risk genes when integrating whole-genome CNVs and whole-exome sequencing data. We also identified several CNVs that include known ASD genes (SHANK3, CDH10, CSMD1) or genes involved in nervous system development (NYAP2, ST6GAL2, GRM6). Besides, our study also implicated Contactins-NYAPs-WAVE1 pathway in ASD pathogenesis. Our findings identify ASD-related CNVs in a Chinese population and implicate novel ASD risk genes and related pathway for further study.
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.|Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Mental Health Center of Shandong Province, Jinan, Shandong, China.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Xun
authors.affiliation: Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ou
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Hefei, Anhui, China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Tianyun
authors.initials: T
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xia
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Bai
authors.affiliation: Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tian
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Zhao
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Hefei, Anhui, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.|The Global Clinical and Translational Research Institute, Bethesda, Maryland, USA.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Children's Development Behavior Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zou
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.|Collaborative Innovation Center for Genetics and Development, Shanghai, China.|College of Life Science and Technology, Xinjiang University, Xinjiang, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D000328:Adult; D044466:Asian People; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D002877:Chromosomes, Human / Q000235:genetics*; D059472:Exome; D005260:Female; D018628:Gene Dosage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male