Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach
Open accessAbstract
Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene‐set analyses, extend the knowledge gained from genome‐wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway‐level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain‐relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross‐method convergence in evaluating pathway analysis results. © 2016 Wiley Periodicals, Inc.
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“Axonal guidance and reelin signaling are important pathways for nervous system development and have been implicated in neuropsychiatric disorders such as bipolar, SCZ, and ADHD [64–68]”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [64]
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Elam, K. K., Clifford, S., Shaw, D. S., Wilson, M. N., & Lemery-Chalfant, K. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0513-7 · Cited by 23 · see citing works
- Authors
- Mooney, M. A., McWeeney, S. K., Faraone, S. V., Hinney, A., Hebebrand, J., IMAGE2 Consortium, German ADHD GWAS Group, Nigg, J. T., & Wilmot, B.
- Affiliations
- Oregon Health & Science University (US)
- SUNY Upstate Medical University (US)
- Essen University Hospital (DE)
- Corresponding author
- Wilmot, Beth
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2016-03-22
- Volume
- 171
- Issue
- 6
- Pages
- 815-826
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC4983253
- OpenAlex
- W2307346192
- Cited by
- 48
- References
- 79
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 1
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Site cant be reached (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- St Andrews Research Repository (St Andrews Research Repository) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Institute of Mental Health (MH099064, R13MH059126, R01MH094469)
- California Department of Fish and Game (HE1446/9‐1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- attention deficit hyperactivity disorder, pathway analysis, gene set analysis, ensemble methods, genome-wide association study, Psychiatric Genomics Consortium, RhoA signaling, glycosaminoglycan synthesis, fibroblast growth factor receptor, potassium channel genes, neurotransmitter release, neurite outgrowth, axon guidance
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Genotype, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Databases, Nucleic Acid, Genome-Wide Association Study
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