title: Chromatin remodeling gene EZH2 involved in the genetic etiology of autism in Chinese Han population.
abstract: Autism spectrum disorder (ASD) is a group of severe neurodevelopmental disorders. Epigenetic factors play a critical role in the etiology of ASD. Enhancer of zest homolog 2 (EZH2), which encodes a histone methyltransferase, plays an important role in the process of chromatin remodeling during neurodevelopment. Further, EZH2 is located in chromosome 7q35-36, which is one of the linkage regions for autism. However, the genetic relationship between autism and EZH2 remains unclear. To investigate the association between EZH2 and autism in Chinese Han population, we performed a family-based association study between autism and three tagged single nucleotide polymorphisms (SNPs) that covered 95.4% of the whole region of EZH2. In the discovery cohort of 239 trios, two SNPs (rs740949 and rs6464926) showed a significant association with autism. To decrease false positive results, we expanded the sample size to 427 trios. A SNP (rs6464926) was significantly associated with autism even after Bonferroni correction (p=0.008). Haplotype G-T (rs740949 and rs6464926) was a risk factor for autism (Z=2.655, p=0.008, Global p=0.024). In silico function prediction for SNPs indicated that these two SNPs might be regulatory SNPs. Expression pattern of EZH2 showed that it is highly expressed in human embryonic brains. In conclusion, our findings demonstrate that EZH2 might contribute to the genetic etiology of autism in Chinese Han population.
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: You
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Zhiliu
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Jia
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China. Electronic address: ljyuch@bjmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, PR China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, PR China. Electronic address: daizhang@bjmu.edu.cn.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China. Electronic address: lifangwang@bjmu.edu.cn.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
mesh_terms: D044466:Asian People; D001321:Autistic Disorder / Q000208:ethnology / Q000235:genetics*; D002648:Child; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D003198:Computer Simulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: Autism; Chromatin remodeling gene; EZH2; Family-based association test