Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/181897 |
Resumo: | 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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Pagerols, MireiaRicharte, VanesaSánchez-Mora, CristinaRovira, PaulaSoler Artigas, MaríaGarcia-Martínez, IrisCalvo-Sánchez, EvaCorrales, MontserratSilva, Bruna Santos daMota, Nina RothVictor, Marcelo MoraesRohde, Luis Augusto PaimGrevet, Eugenio HorácioBau, Claiton Henrique DottoCormand, BruCasas, MiguelRamos-Quiroga, Josep AntoniRibasés, Marta2018-09-13T02:31:27Z20182045-2322http://hdl.handle.net/10183/181897001074363Methylphenidate (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.application/pdfengScientific reports. London. Vol. 8 (2018), 1881, 11 p.Transtorno do déficit de atenção com hiperatividadeMetilfenidatoAdultoPolimorfismo de nucleotídeo únicoIntegrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorderEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001074363.pdfTexto completo (inglês)application/pdf882972http://www.lume.ufrgs.br/bitstream/10183/181897/1/001074363.pdf89fd8c2e9b3efe36db6bc6d3f222b43eMD51TEXT001074363.pdf.txt001074363.pdf.txtExtracted Texttext/plain64607http://www.lume.ufrgs.br/bitstream/10183/181897/2/001074363.pdf.txtff3b6c3fa0fad827059a2e1439f43cb7MD52THUMBNAIL001074363.pdf.jpg001074363.pdf.jpgGenerated Thumbnailimage/jpeg2002http://www.lume.ufrgs.br/bitstream/10183/181897/3/001074363.pdf.jpg10335a8a60e7c5a698c774ca9397fe7fMD5310183/1818972022-10-28 04:48:22.102966oai:www.lume.ufrgs.br:10183/181897Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-10-28T07:48:22Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder |
title |
Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder |
spellingShingle |
Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder Pagerols, Mireia Transtorno do déficit de atenção com hiperatividade Metilfenidato Adulto Polimorfismo de nucleotídeo único |
title_short |
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_sort |
Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder |
author |
Pagerols, Mireia |
author_facet |
Pagerols, Mireia Richarte, Vanesa Sánchez-Mora, Cristina Rovira, Paula Soler Artigas, María Garcia-Martínez, Iris Calvo-Sánchez, Eva Corrales, Montserrat Silva, Bruna Santos da Mota, Nina Roth Victor, Marcelo Moraes Rohde, Luis Augusto Paim Grevet, Eugenio Horácio Bau, Claiton Henrique Dotto Cormand, Bru Casas, Miguel Ramos-Quiroga, Josep Antoni Ribasés, Marta |
author_role |
author |
author2 |
Richarte, Vanesa Sánchez-Mora, Cristina Rovira, Paula Soler Artigas, María Garcia-Martínez, Iris Calvo-Sánchez, Eva Corrales, Montserrat Silva, Bruna Santos da Mota, Nina Roth Victor, Marcelo Moraes Rohde, Luis Augusto Paim Grevet, Eugenio Horácio Bau, Claiton Henrique Dotto Cormand, Bru Casas, Miguel Ramos-Quiroga, Josep Antoni Ribasés, Marta |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Pagerols, Mireia Richarte, Vanesa Sánchez-Mora, Cristina Rovira, Paula Soler Artigas, María Garcia-Martínez, Iris Calvo-Sánchez, Eva Corrales, Montserrat Silva, Bruna Santos da Mota, Nina Roth Victor, Marcelo Moraes Rohde, Luis Augusto Paim Grevet, Eugenio Horácio Bau, Claiton Henrique Dotto Cormand, Bru Casas, Miguel Ramos-Quiroga, Josep Antoni Ribasés, Marta |
dc.subject.por.fl_str_mv |
Transtorno do déficit de atenção com hiperatividade Metilfenidato Adulto Polimorfismo de nucleotídeo único |
topic |
Transtorno do déficit de atenção com hiperatividade Metilfenidato Adulto Polimorfismo de nucleotídeo único |
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. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-09-13T02:31:27Z |
dc.date.issued.fl_str_mv |
2018 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/181897 |
dc.identifier.issn.pt_BR.fl_str_mv |
2045-2322 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001074363 |
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2045-2322 001074363 |
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http://hdl.handle.net/10183/181897 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Scientific reports. London. Vol. 8 (2018), 1881, 11 p. |
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openAccess |
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