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学科主题: 精神卫生
题名:
Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: Genome-wide association study of both common and rare variants
作者: Yang, Li1,2; Neale, Benjamin M.3,4; Liu, Lu1,2; Lee, S. Hong5; Wray, Naomi R.5; Ji, Ning1,2; Li, Haimei1,2; Qian, Qiujin1,2; Wang, Dongliang6; Li, Jun7; Faraone, Stephen V.6; Wang, Yufeng1,2; Psychiat GWAS Consortium ADHD1
关键词: ADHD ; GWAS ; pathway ; neurodevelopment
刊名: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
发表日期: 2013-07-01
DOI: 10.1002/ajmg.b.32169
卷: 162B, 期:5, 页:419-430
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity ; Psychiatry
研究领域[WOS]: Genetics & Heredity ; Psychiatry
关键词[WOS]: DEFICIT/HYPERACTIVITY DISORDER ; BIPOLAR DISORDER ; SCHIZOPHRENIA ; LINKAGE ; GENE ; POLYMORPHISM ; METAANALYSIS ; SCAN ; ADHD ; DUPLICATIONS
英文摘要:

Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P=0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P=0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P=0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD′s etiology. (c) 2013 Wiley Periodicals, Inc.

语种: 英语
所属项目编号: 30800302 ; 81071109 ; 200802073 ; NCET-11-0013 ; 2007BAI17B03 ; R13MH059126 ; R01MH62873 ; U01MH085518 ; R01MH081803 ; U01MH085515 ; K23MH066275-01 ; R01MH58277 ; FT0991360 ; 1011506 ; 1047956 ; 443036 ; KFO 125 ; SFB 581 ; GRK 1156 ; ME 1923/5-1 ; ME 1923/5-3 ; GRK 1389 ; BMBF 01GV0605 ; MOP 64277 ; 44070 ; 74699 ; SCHA 542/10-3
项目资助者: National Natural Science Foundation of China ; Chinese Ministry of Health ; Ministry of Education Program for New Century Excellent Talents in University ; Ministry of Science and Technology ; National Institute of Health ; Australian Research council ; Australian National Health and Medical Research Council ; Children&prime ; s Hospital of Philadelphia ; Affymetrix Power Award ; Sidney Sax Public Health Fellowship ; Wellcome Trust, UK ; UMC Utrecht Genvlag Grant ; Radboud University ; Nijmegen Medical Centre ; Deutsche Forschungsgemeinschaft ; BundesministeriumfurBildung und Forschung ; Canadian Institutes of Health Research
WOS记录号: WOS:000320549100001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52026
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China
2.Peking Univ Sixth Hosp, Inst Mental Hlth, Beijing 100191, Peoples R China
3.Broad Inst Harvard & MIT, Cambridge, MA USA
4.Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
5.Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia
6.SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA
7.Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China

Recommended Citation:
Yang, Li,Neale, Benjamin M.,Liu, Lu,et al. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: Genome-wide association study of both common and rare variants[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS,2013,162B(5):419-430.
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