Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder

Mireia Pagerols, Vanesa Richarte, Cristina Sánchez-Mora, Paula Rovira, María Soler Artigas, Iris Garcia-Martínez, Eva Calvo-Sánchez, Montse Corrales, Bruna Santos Da Silva, Nina Roth Mota, Marcelo Moraes Victor, Luis Augusto Rohde, Eugenio Horacio Grevet, Claiton Henrique Dotto Bau, Bru Cormand, Miguel Casas, Josep Antoni Ramos-Quiroga, Marta Ribasés

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3 Citations (Scopus)

Abstract

© 2018 The Author(s). 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.
Original languageEnglish
Article number1881
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 1 Dec 2018

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    Pagerols, M., Richarte, V., Sánchez-Mora, C., Rovira, P., Soler Artigas, M., Garcia-Martínez, I., Calvo-Sánchez, E., Corrales, M., Da Silva, B. S., Mota, N. R., Victor, M. M., Rohde, L. A., Grevet, E. H., Bau, C. H. D., Cormand, B., Casas, M., Ramos-Quiroga, J. A., & Ribasés, M. (2018). Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder. Scientific Reports, 8, [1881]. https://doi.org/10.1038/s41598-018-20194-7