Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: Genome‐wide association study of both common and rare variants
Open accessAbstract
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.
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Many studies of complex neuropsychiatric disorders have concluded that disease-causing variants are often clustered in protein-interaction networks with a high degree of connectivity among themselves and that these clustered networks are often enriched with functional pathways relevant to brain functions.
“Many studies of complex neuropsychiatric disorders have also concluded that disease-causing variants are often clustered in protein-interaction networks with a high degree of connectivity among themselves and that these clustered networks are often enriched with functional pathways relevant to brain functions [72–80].”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [80]
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- Authors
- Yang, L., Neale, B. M., Liu, L., Lee, S. H., Wray, N. R., Ji, N., Li, H., Qian, Q., Wang, D., Li, J., Faraone, S. V., Wang, Y., & Psychiatric GWAS Consortium: ADHD Subgroup
- Affiliations
- Peking University Sixth Hospital (CN)
- Broad Institute (US)
- The University of Queensland (AU)
- SUNY Upstate Medical University (US)
- Beijing Normal University (CN)
- Corresponding author
- Faraone, Stephen V.
- Wang, Yufeng
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2013-05-31
- Volume
- 162
- Issue
- 5
- Pages
- 419-430
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC4321789
- OpenAlex
- W2033598166
- Cited by
- 171
- References
- 43
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 13 · 2020: 10 · 2019: 21 · 2018: 18 · 2017: 15 · 2016: 22 · 2015: 24 · 2014: 19
- FWCI
- 15.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DuEPublico (University of Duisburg-Essen) (submittedVersion)
- EPubDev Repository (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- RUNE (Research UNE) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Eli Lilly and Company
- Pfizer
- Children's Hospital of Philadelphia
- Wellcome Trust
- University of Oxford
- Deutsche Forschungsgemeinschaft (ME 1923/5-3, 1923/5-3, SFB 581, KFO125, ME 1923/5-1, 1923/5-1, GRK 1156, SCHA 542/10-3)
- National Natural Science Foundation of China (30800302, 81071109)
- Radboud Universiteit
- Bundesministerium für Bildung und Forschung (BMBF 01GV0605, 01GV0605)
- Universitair Medisch Centrum Utrecht
- National Institutes of Health (5k23mh066275-05)
- Canadian Institutes of Health Research (44070, MOP44070, 64277_1, 64277, 74699, 74699_1)
- Medical Research Council
- Australian Research Council (FT0991360)
- National Health and Medical Research Council (443036, 1047956, 1011506)
- Program for New Century Excellent Talents in University (NCET-11-, NCET-11-0013)
- National Institute of Mental Health (R01MH058277, R01 MH 62873, U01MH085518, R01MH081803, R01MH58277, R01MH062873, K23MH066275, K23MH066275-01, R13MH059126, U01MH085515)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD004612)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, polygenic inheritance, copy number variation, rare variants, single nucleotide polymorphisms, SNP heritability, genetic correlation, neurodevelopmental pathways, Han Chinese, genetic architecture
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans, Male, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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