Garcia Martínez, IrisSánchez-Mora, CristinaSoler Artigas, MaríaRovira, PaulaPagerols, MireiaCorrales, MontseCalvo Sánchez, EvaRicharte, VanesaBustamante Pineda, MarionaSunyer Deu, JordiCormand, BruCasas, MiguelRamos Quiroga, Josep AntoniRibasés, Marta2017-11-272017-11-272017Garcia-Martínez I, Sánchez-Mora C, Soler Artigas M, Rovira P, Pagerols M, Corrales M et al. Gene-wide association study reveals RNF122 ubiquitin ligase as a novel susceptibility gene for attention deficit hyperactivity disorder. Sci Rep. 2017 Jul 14;7(1):5407. DOI: 10.1038/s41598-017-05514-72045-2322http://hdl.handle.net/10230/33345Attention 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.application/pdfeng© Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-017-05514-7Behavioural geneticsGenome-wide association studiesinfo:eu-repo/semantics/openAccess