title: Multiple epigenetic factors predict the attention deficit/hyperactivity disorder among the Chinese Han children.
abstract: Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case-control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder.
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, PR China. Electronic address: xuyixuyi3734@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, Anhui Province, 230031, PR China. Electronic address: chenxt@ustc.edu.cn.
authors.forename: Xiang-Tao
authors.initials: XT
authors.lastname: Chen
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, PR China. Electronic address: 457662345@qq.com.
authors.forename: Man
authors.initials: M
authors.lastname: Luo
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, PR China. Electronic address: yuqingtang3@gmail.com.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Biostatistics and Data Management Core, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. Electronic address: georgexzh@gmail.com.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, PR China. Electronic address: wude7310@sohu.com.
authors.forename: De
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Child Neurology, Anhui Provincial Children's Hospital, Hefei, Anhui Province, 230031, PR China. Electronic address: 0111yangbin@sina.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, PR China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China. Electronic address: ruandy@ustc.edu.cn.
authors.forename: Di-Yun
authors.initials: DY
authors.lastname: Ruan
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui Province, 230009, PR China. Electronic address: wanghl@hfut.edu.cn.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wang
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002681:China / Q000453:epidemiology / Q000208:ethnology; D018899:CpG Islands / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D007854:Lead / Q000633:toxicity; D016015:Logistic Models; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics; D013223:Statistics as Topic
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D011954:Receptors, Dopamine; C493214:SLC6A3 protein, human; D007854:Lead; C098075:DNA modification methylase CcrM; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D051548:Histone Acetyltransferases; C487137:KAT6B protein, human; D006655:Histone Deacetylases
keywords: ADHD; DNA methylation; Epigenetic; Histone acetylation; MeCP2