Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder
Garcia Martínez, I (Hospital Universitari Vall d'Hebron)
Sánchez Mora, C. (Hospital Universitari Vall d'Hebron)
Pagerols, Mireia (Hospital Universitari Vall d'Hebron)
Richarte, Vanesa (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Corrales, Montserrat (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Fadeuilhe, Christian (Hospital Universitari Vall d'Hebron)
Cormand, Bru (Institut de Recerca Sant Joan de Déu)
Casas, M. (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Ramos-Quiroga, Josep Antoni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Ribasés, M.. (Hospital Universitari Vall d'Hebron)

Data:	2016
Resum:	Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by impairment to sustain attention and inability to control impulses and activity level. The etiology of ADHD is complex, with an estimated heritability of 70-80%. Under the hypothesis that alterations in the processing or target binding of microRNAs (miRNAs) may result in functional alterations predisposing to ADHD, we explored whether common polymorphisms potentially affecting miRNA-mediated regulation are involved in this psychiatric disorder. We performed a comprehensive association study focused on 134 miRNAs in 754 ADHD subjects and 766 controls and found association between the miR-34b/c locus and ADHD. Subsequently, we provided preliminary evidence for overexpression of the miR-34c-3p mature form in peripheral blood mononuclear cells of ADHD subjects. Next, we tested the effect on gene expression of single-nucleotide polymorphisms within the ADHD-associated region and found that rs4938923 in the promoter of the pri-miR-34b/c tags cis expression quantitative trait loci for both miR-34b and miR-34c and has an impact on the expression levels of 681 transcripts in trans, including genes previously associated with ADHD. This gene set was enriched for miR-34b/c binding sites, functional categories related to the central nervous system, such as axon guidance or neuron differentiation, and serotonin biosynthesis and signaling canonical pathways. Our results provide preliminary evidence for the contribution to ADHD of a functional variant in the pri-miR-34b/c promoter, possibly through dysregulation of the expression of mature forms of miR-34b and miR-34c and some target genes. These data highlight the importance of abnormal miRNA function as a potential epigenetic mechanism contributing to ADHD.
Ajuts:	European Commission 602805 European Commission 667302 European Commission 643051 Instituto de Salud Carlos III CP09/00119 Instituto de Salud Carlos III CPII15/00023 Instituto de Salud Carlos III PI11/00571 Instituto de Salud Carlos III PI11/01629 Instituto de Salud Carlos III PI12/01139 Instituto de Salud Carlos III PI14/01700 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR1357 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR0932 Ministerio de Economía y Competitividad SAF2012-33484 Ministerio de Economía y Competitividad SAF2015-68341-R Ministerio de Economía y Competitividad CD15/0019
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Translational psychiatry, Vol. 6 (08 2016) , p. e879, ISSN 2158-3188

DOI: 10.1038/tp.2016.151
PMID: 27576168

9 p, 483.0 KB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats