Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach. Issue 6 (22nd March 2016)

• Record Type: Journal Article
• Authors: Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth
• Other Names: Faraone Stephen V. investigator.; Romanos Marcel investigator.; Warnke Andreas investigator.; Reif Andreas investigator.; Walitza Susanne investigator.; Roeyers Herbert investigator.; Franke Barbara investigator.; Buitelaar Jan K. investigator.; Lesch Klaus‐Peter investigator.; Kent Lindsey investigator.; Vasquez Alejandro Arias investigator.; Thapar Anita investigator.; Martin Joanna investigator.; O'Donovan Michael C. investigator.; Owen Michael J. investigator.; Williams Nigel investigator.; Holmans Peter investigator.; Langley Kate investigator.; Freitag Christine investigator.; Lambregts‐Rommelse Nanda investigator.; Anney Richard J.L. investigator.; Mulligan Aisling investigator.; Rothenberger Aribert investigator.; Steinhausen Hans‐Christoph investigator.; Gill Michael investigator.; Asherson Philip investigator.; Nguyen T. Trang investigator.; Biederman Joseph investigator.; Doyle Alysa E. investigator.; Romanos Jasmin investigator.; Rivero Olga investigator.; Palmason Haukur investigator.; Meyer Jobst investigator.; Renner Tobias J. investigator.; Hinney Anke investigator.; Albayrak Özgür investigator.; Volckmar Anna‐Lena investigator.; Hebebrand Johannes investigator.; Dempfle Astrid investigator.; Cichon Sven investigator.; Hoffmann Per investigator.; Nöthen Markus M. investigator.; Schreiber Stefan investigator.; Möbus Susanne investigator.; Wichmann H.‐Erich investigator.; Herpertz‐Dahlmann Beate investigator.; Sinzig Judith investigator.; Lehmkuhl Gerd investigator.; Renner Tobias J. investigator.; Romanos Marcel investigator.; Schimmelmann Benno G. investigator.;
• Is Part Of: American journal of medical genetics. Volume 171:Issue 6(2016)
• Page Start: 815
• Page End: 826
• Publication Date: 2016-03-22
• Subjects: ADHD -- pathway analyses -- GWAS; Neuropsychiatry -- Periodicals; Medical genetics -- Periodicals; 616.8904205
• DOI: 10.1002/ajmg.b.32446
• Languages: English
• ISSNs: 1552-4841

Abstract

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.