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

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...

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Autores principales: Pagerols, Mireia, Richarte, Vanesa, Sánchez-Mora, Cristina, Rovira, Paula, Soler Artigas, María, Garcia-Martínez, Iris, Calvo-Sánchez, Eva, Corrales, Montse, da Silva, Bruna Santos, Mota, Nina Roth, Victor, Marcelo Moraes, Rohde, Luis Augusto, Grevet, Eugenio Horacio, Bau, Claiton Henrique Dotto, Cormand, Bru, Casas, Miguel, Ramos-Quiroga, Josep Antoni, Ribasés, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789875/
https://www.ncbi.nlm.nih.gov/pubmed/29382897
http://dx.doi.org/10.1038/s41598-018-20194-7
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author Pagerols, Mireia
Richarte, Vanesa
Sánchez-Mora, Cristina
Rovira, Paula
Soler Artigas, María
Garcia-Martínez, Iris
Calvo-Sánchez, Eva
Corrales, Montse
da Silva, Bruna Santos
Mota, Nina Roth
Victor, Marcelo Moraes
Rohde, Luis Augusto
Grevet, Eugenio Horacio
Bau, Claiton Henrique Dotto
Cormand, Bru
Casas, Miguel
Ramos-Quiroga, Josep Antoni
Ribasés, Marta
author_facet Pagerols, Mireia
Richarte, Vanesa
Sánchez-Mora, Cristina
Rovira, Paula
Soler Artigas, María
Garcia-Martínez, Iris
Calvo-Sánchez, Eva
Corrales, Montse
da Silva, Bruna Santos
Mota, Nina Roth
Victor, Marcelo Moraes
Rohde, Luis Augusto
Grevet, Eugenio Horacio
Bau, Claiton Henrique Dotto
Cormand, Bru
Casas, Miguel
Ramos-Quiroga, Josep Antoni
Ribasés, Marta
author_sort Pagerols, Mireia
collection PubMed
description 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.
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spelling pubmed-57898752018-02-15 Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder Pagerols, Mireia Richarte, Vanesa Sánchez-Mora, Cristina Rovira, Paula Soler Artigas, María Garcia-Martínez, Iris Calvo-Sánchez, Eva Corrales, Montse da Silva, Bruna Santos Mota, Nina Roth Victor, Marcelo Moraes Rohde, Luis Augusto Grevet, Eugenio Horacio Bau, Claiton Henrique Dotto Cormand, Bru Casas, Miguel Ramos-Quiroga, Josep Antoni Ribasés, Marta Sci Rep Article 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. Nature Publishing Group UK 2018-01-30 /pmc/articles/PMC5789875/ /pubmed/29382897 http://dx.doi.org/10.1038/s41598-018-20194-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pagerols, Mireia
Richarte, Vanesa
Sánchez-Mora, Cristina
Rovira, Paula
Soler Artigas, María
Garcia-Martínez, Iris
Calvo-Sánchez, Eva
Corrales, Montse
da Silva, Bruna Santos
Mota, Nina Roth
Victor, Marcelo Moraes
Rohde, Luis Augusto
Grevet, Eugenio Horacio
Bau, Claiton Henrique Dotto
Cormand, Bru
Casas, Miguel
Ramos-Quiroga, Josep Antoni
Ribasés, Marta
Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
title Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
title_full Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
title_fullStr Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
title_full_unstemmed Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
title_short Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
title_sort integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789875/
https://www.ncbi.nlm.nih.gov/pubmed/29382897
http://dx.doi.org/10.1038/s41598-018-20194-7
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