학술논문
Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach
Document Type
Article
Author
Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Faraone, Stephen V.; Romanos, Marcel; Warnke, Andreas; Reif, Andreas; Walitza, Susanne; Roeyers, Herbert; Franke, Barbara; Buitelaar, Jan K.; Lesch, Klaus‐Peter; Kent, Lindsey; Vasquez, Alejandro Arias; Thapar, Anita; Martin, Joanna; O'Donovan, Michael C.; Owen, Michael J.; Williams, Nigel; Holmans, Peter; Langley, Kate; Freitag, Christine; Lambregts‐Rommelse, Nanda; Anney, Richard J.L.; Mulligan, Aisling; Rothenberger, Aribert; Steinhausen, Hans‐Christoph; Gill, Michael; Asherson, Philip; Nguyen, T. Trang; Biederman, Joseph; Doyle, Alysa E.; Romanos, Jasmin; Rivero, Olga; Palmason, Haukur; Meyer, Jobst; Renner, Tobias J.; Hinney, Anke; Albayrak, Özgür; Volckmar, Anna‐Lena; Hebebrand, Johannes; Dempfle, Astrid; Cichon, Sven; Hoffmann, Per; Nöthen, Markus M.; Schreiber, Stefan; Möbus, Susanne; Wichmann, H.‐Erich; Herpertz‐Dahlmann, Beate; Sinzig, Judith; Lehmkuhl, Gerd; Renner, Tobias J.; Romanos, Marcel; Schimmelmann, Benno G.; Nigg, Joel T.; Wilmot, Beth
Source
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics; September 2016, Vol. 171 Issue: 6 p815-826, 12p
Subject
Language
ISSN
15524841; 1552485X
Abstract
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.