Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
| Autor: | Josep Antoni Ramos-Quiroga, Nina Roth Mota, Iris Garcia-Martínez, Marta Ribasés, Claiton H.D. Bau, Vanesa Richarte, Eugenio H. Grevet, Bruna Santos da Silva, Paula Rovira, Bru Cormand, Marcelo M. Victor, María Soler Artigas, Luis Augusto Rohde, Miguel Casas, Cristina Sánchez-Mora, Montse Corrales, Mireia Pagerols, Eva Calvo-Sánchez |
|---|---|
| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Trastorns per dèficit d'atenció amb hiperactivitat en els infants lcsh:Medicine Genome-wide association study Bioinformatics Attention deficit disorder with hyperactivity in children 0302 clinical medicine Human genetics Polymorphism (computer science) Child lcsh:Science Polimorfismo de nucleotídeo único Genètica humana Multidisciplinary Adulto Methylphenidate Genomics Human brain Transtorno do déficit de atenção com hiperatividade Treatment Outcome medicine.anatomical_structure Child Preschool Cohort Female Metilfenidato medicine.drug Nervous system Adolescent Single-nucleotide polymorphism Polymorphism Single Nucleotide Article 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center mental disorders medicine Humans Attention deficit hyperactivity disorder Sistema nerviós Attention-deficit-disordered children Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] business.industry lcsh:R medicine.disease Trastorns per dèficit d'atenció en els infants 030104 developmental biology Attention Deficit Disorder with Hyperactivity Expression quantitative trait loci Central Nervous System Stimulants lcsh:Q business 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Scientific Reports, 8 Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) Dipòsit Digital de la UB Universidad de Barcelona Scientific Reports Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Repositório Institucional da UFRGS Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 2045-2322 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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