Li Yang and Benjamin M. Neale contributed equally to this study.
Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: Genome-wide association study of both common and rare variants
Article first published online: 31 MAY 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 162, Issue 5, pages 419–430, July 2013
How to Cite
2013. Polygenic Transmission and Complex Neuro Developmental Network for Attention Deficit Hyperactivity Disorder: Genome-Wide Association Study of Both Common and Rare Variants. Am J Med Genet Part B 162B:419–430., , , , , , , , , , , , .
For Psychiatric GWAS Consortium-ADHD subgroup authors see Supplementary Materials.
- Issue published online: 18 JUN 2013
- Article first published online: 31 MAY 2013
- Manuscript Accepted: 19 APR 2013
- Manuscript Received: 17 MAR 2013
- National Natural Science Foundation of China. Grant Numbers: 30800302, 81071109
- Chinese Ministry of Health. Grant Number: 200802073
- Ministry of Education Program for New Century Excellent Talents in University. Grant Number: NCET-11-0013
- Ministry of Science and Technology. Grant Number: 2007BAI17B03
- National Institute of Health Grants. Grant Numbers: R13MH059126, R01MH62873, U01MH085518, R01MH081803, U01MH085515, K23MH066275-01, R01MH58277
- Funding from the Australian Research council. Grant Number: FT0991360
- Australian National Health and Medical Research Council. Grant Numbers: 1011506, 1047956
- Children's Hospital of Philadelphia
- Affymetrix Power Award
- Sidney Sax Public Health Fellowship. Grant Number: 443036
- Wellcome Trust, UK
- UMC Utrecht Genvlag Grant and Internal Grant of Radboud University, Nijmegen Medical Centre
- Deutsche Forschungsgemeinschaft. Grant Numbers: KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389
- J. Meyer. Grant Number: SCHA 542/10-3
- BundesministeriumfürBildung und Forschung. Grant Number: BMBF 01GV0605
- Canadian Institutes of Health Research. Grant Numbers: MOP 64277, 44070, 74699
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. © 2013 Wiley Periodicals, Inc.