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https://hdl.handle.net/1959.11/18859
Title: | Polygenic Transmission and Complex Neuro Developmental Network for Attention Deficit Hyperactivity Disorder: Genome-Wide Association Study of Both Common and Rare Variants | Contributor(s): | Yang, Li (author); Neale, Benjamin M (author); Faraone, Stephen V (author); Wang, Yufeng (author); Liu, Lu (author); Lee, Sang Hong (author); Wray, Naomi R (author); Ji, Ning (author); Li, Haimei (author); Qian, Qiujin (author); Wang, Dongliang (author); Li, Jun (author) | Publication Date: | 2013 | Open Access: | Yes | DOI: | 10.1002/ajmg.b.32169![]() |
Handle Link: | https://hdl.handle.net/1959.11/18859 | Abstract: | 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. | Publication Type: | Journal Article | Grant Details: | NHMRC/1011506 NHMRC/1047956 |
Source of Publication: | American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 162(5), p. 419-430 | Publisher: | John Wiley & Sons, Inc | Place of Publication: | United States of America | ISSN: | 1552-485X 1552-4841 |
Fields of Research (FoR) 2008: | 110319 Psychiatry (incl. Psychotherapy) 060408 Genomics 060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics) |
Fields of Research (FoR) 2020: | 320221 Psychiatry (incl. psychotherapy) 310509 Genomics 310506 Gene mapping |
Socio-Economic Objective (SEO) 2008: | 920110 Inherited Diseases (incl. Gene Therapy) 970106 Expanding Knowledge in the Biological Sciences 970111 Expanding Knowledge in the Medical and Health Sciences |
Socio-Economic Objective (SEO) 2020: | 280102 Expanding knowledge in the biological sciences | Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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Appears in Collections: | Journal Article |
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