Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood-onset neurodevelopmental condition characterized by pervasive impairment of attention, hyperactivity, and/or impulsivity that can persist into adulthood. The aetiology of ADHD is complex and multifactorial and, despite the wealth...

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Detalhes bibliográficos
Autores: García-Martinez, Iris|||0000-0001-6656-3322, Sánchez-Mora, Cristina|||0000-0003-4211-1107, Soler Artigas, María|||0000-0002-3213-1107, Rovira, Paula|||0000-0003-2177-8412, Pagerols, Mireia|||0000-0003-0856-6247, Corrales, Montserrat|||0000-0002-7428-1402, Calvo-Sánchez, Eva|||0000-0001-8211-6047, Richarte, Vanesa|||0000-0001-7327-318X, Bustamante, Mariona|||0000-0003-0127-2860, Sunyer, Jordi, Cormand, Bru|||0000-0001-5318-4382, Casas Brugué, Miquel|||0000-0003-3496-8522, Ramos-Quiroga, Josep Antoni|||0000-0003-1622-0350, Ribasés Haro, Marta|||0000-0003-1039-1116
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253925
Acesso em linha:https://ddd.uab.cat/record/253925
https://dx.doi.org/urn:doi:10.1038/s41598-017-05514-7
Access Level:acceso abierto
Descrição
Resumo:Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood-onset neurodevelopmental condition characterized by pervasive impairment of attention, hyperactivity, and/or impulsivity that can persist into adulthood. The aetiology of ADHD is complex and multifactorial and, despite the wealth of evidence for its high heritability, genetic studies have provided modest evidence for the involvement of specific genes and have failed to identify consistent and replicable results. Due to the lack of robust findings, we performed gene-wide and pathway enrichment analyses using pre-existing GWAS data from 607 persistent ADHD subjects and 584 controls, produced by our group. Subsequently, expression profiles of genes surpassing a follow-up threshold of P-value < 1e-03 in the gene-wide analyses were tested in peripheral blood mononucleated cells (PBMCs) of 45 medication-naive adults with ADHD and 39 healthy unrelated controls. We found preliminary evidence for genetic association between RNF122 and ADHD and for its overexpression in adults with ADHD. RNF122 encodes for an E3 ubiquitin ligase involved in the proteasome-mediated processing, trafficking, and degradation of proteins that acts as an essential mediator of the substrate specificity of ubiquitin ligation. Thus, our findings support previous data that place the ubiquitin-proteasome system as a promising candidate for its involvement in the aetiology of ADHD.

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