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

Abstract 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 th...

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Autores principales:	Iris Garcia-Martínez, Cristina Sánchez-Mora, María Soler Artigas, Paula Rovira, Mireia Pagerols, Montse Corrales, Eva Calvo-Sánchez, Vanesa Richarte, Mariona Bustamante, Jordi Sunyer, Bru Cormand, Miquel Casas, Josep Antoni Ramos-Quiroga, Marta Ribasés
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a48209a64574e1da65f24dd7475a59c
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spelling	oai:doaj.org-article:3a48209a64574e1da65f24dd7475a59c2021-12-02T11:40:21ZGene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder10.1038/s41598-017-05514-72045-2322https://doaj.org/article/3a48209a64574e1da65f24dd7475a59c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05514-7https://doaj.org/toc/2045-2322Abstract 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.Iris Garcia-MartínezCristina Sánchez-MoraMaría Soler ArtigasPaula RoviraMireia PagerolsMontse CorralesEva Calvo-SánchezVanesa RicharteMariona BustamanteJordi SunyerBru CormandMiquel CasasJosep Antoni Ramos-QuirogaMarta RibasésNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Iris Garcia-Martínez Cristina Sánchez-Mora María Soler Artigas Paula Rovira Mireia Pagerols Montse Corrales Eva Calvo-Sánchez Vanesa Richarte Mariona Bustamante Jordi Sunyer Bru Cormand Miquel Casas Josep Antoni Ramos-Quiroga Marta Ribasés Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder
description	Abstract 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.
format	article
author	Iris Garcia-Martínez Cristina Sánchez-Mora María Soler Artigas Paula Rovira Mireia Pagerols Montse Corrales Eva Calvo-Sánchez Vanesa Richarte Mariona Bustamante Jordi Sunyer Bru Cormand Miquel Casas Josep Antoni Ramos-Quiroga Marta Ribasés
author_facet	Iris Garcia-Martínez Cristina Sánchez-Mora María Soler Artigas Paula Rovira Mireia Pagerols Montse Corrales Eva Calvo-Sánchez Vanesa Richarte Mariona Bustamante Jordi Sunyer Bru Cormand Miquel Casas Josep Antoni Ramos-Quiroga Marta Ribasés
author_sort	Iris Garcia-Martínez
title	Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder
title_short	Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder
title_full	Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder
title_fullStr	Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder
title_full_unstemmed	Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder
title_sort	gene-wide association study reveals rnf122 ubiquitin ligase as a novel susceptibility gene for attention deficit hyperactivity disorder
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3a48209a64574e1da65f24dd7475a59c
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Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder

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