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Mooney, M.A.* ; McWeeney, S.K.* ; Faraone, S.V.* ; Hinney, A.* ; Hebebrand, J.* ; IMAGE2 Consortium* ; German ADHD GWAS Group* ; Nigg, J.T.* ; Wilmot, B.* ; EUMODIC Consortium (Wichmann, H.-E.)

Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach.

Am. J. Med. Genet. B 171, 815-826 (2016)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords ADHD; GWAS; pathway analyses
ISSN (print) / ISBN 1552-4841
e-ISSN 0148-7299
Journal American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Quellenangaben Volume: 171, Issue: 6, Pages: 815-826 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)