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Página principal > Artículos > Artículos publicados > Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder |
Fecha: | 2018 |
Resumen: | Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0. 05) was significantly enriched for candidates previously studied in ADHD or treatment outcome. We prioritised the nominally significant SNPs by functional annotation and expression quantitative trait loci (eQTL) analysis in human brain, and we identified 33 SNPs tagging cis -eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies. |
Ayudas: | Ministerio de Economía y Competitividad CD15/00199 Ministerio de Economía y Competitividad MV16/00039 Ministerio de Ciencia e Innovación II14/00018 Ministerio de Ciencia e Innovación CP09/00119 Ministerio de Economía y Competitividad CPII15/00023 Ministerio de Economía y Competitividad PI12/01139 Ministerio de Economía y Competitividad PI14/01700 Ministerio de Economía y Competitividad PI15/01789 Ministerio de Economía y Competitividad PI16/01505 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 SAF2015-68341-R European Commission. Horizon 2020 667302 European Commission. Horizon 2020 643051 |
Derechos: | 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. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Scientific reports, Vol. 8 (january 2018) , ISSN 2045-2322 |
11 p, 1005.6 KB |