Cargando…

Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population. METHODS: A cohort of ADHD 290 patients and 34...

Descripción completa

Detalles Bibliográficos
Autores principales: Gomez-Sanchez, Clara I., Riveiro-Alvarez, Rosa, Soto-Insuga, Victor, Rodrigo, Maria, Tirado-Requero, Pilar, Mahillo-Fernandez, Ignacio, Abad-Santos, Francisco, Carballo, Juan J., Dal-Ré, Rafael, Ayuso, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706690/
https://www.ncbi.nlm.nih.gov/pubmed/26746237
http://dx.doi.org/10.1186/s12993-015-0084-6
_version_ 1782409203465322496
author Gomez-Sanchez, Clara I.
Riveiro-Alvarez, Rosa
Soto-Insuga, Victor
Rodrigo, Maria
Tirado-Requero, Pilar
Mahillo-Fernandez, Ignacio
Abad-Santos, Francisco
Carballo, Juan J.
Dal-Ré, Rafael
Ayuso, Carmen
author_facet Gomez-Sanchez, Clara I.
Riveiro-Alvarez, Rosa
Soto-Insuga, Victor
Rodrigo, Maria
Tirado-Requero, Pilar
Mahillo-Fernandez, Ignacio
Abad-Santos, Francisco
Carballo, Juan J.
Dal-Ré, Rafael
Ayuso, Carmen
author_sort Gomez-Sanchez, Clara I.
collection PubMed
description BACKGROUND: Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population. METHODS: A cohort of ADHD 290 patients and 340 controls aged 6–18 years were included in a case–control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants. RESULTS: After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively. CONCLUSIONS: We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12993-015-0084-6) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4706690
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-47066902016-01-10 Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children Gomez-Sanchez, Clara I. Riveiro-Alvarez, Rosa Soto-Insuga, Victor Rodrigo, Maria Tirado-Requero, Pilar Mahillo-Fernandez, Ignacio Abad-Santos, Francisco Carballo, Juan J. Dal-Ré, Rafael Ayuso, Carmen Behav Brain Funct Research BACKGROUND: Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population. METHODS: A cohort of ADHD 290 patients and 340 controls aged 6–18 years were included in a case–control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants. RESULTS: After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively. CONCLUSIONS: We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12993-015-0084-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-08 /pmc/articles/PMC4706690/ /pubmed/26746237 http://dx.doi.org/10.1186/s12993-015-0084-6 Text en © Gomez-Sanchez et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Gomez-Sanchez, Clara I.
Riveiro-Alvarez, Rosa
Soto-Insuga, Victor
Rodrigo, Maria
Tirado-Requero, Pilar
Mahillo-Fernandez, Ignacio
Abad-Santos, Francisco
Carballo, Juan J.
Dal-Ré, Rafael
Ayuso, Carmen
Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children
title Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children
title_full Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children
title_fullStr Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children
title_full_unstemmed Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children
title_short Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children
title_sort attention deficit hyperactivity disorder: genetic association study in a cohort of spanish children
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706690/
https://www.ncbi.nlm.nih.gov/pubmed/26746237
http://dx.doi.org/10.1186/s12993-015-0084-6
work_keys_str_mv AT gomezsanchezclarai attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT riveiroalvarezrosa attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT sotoinsugavictor attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT rodrigomaria attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT tiradorequeropilar attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT mahillofernandezignacio attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT abadsantosfrancisco attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT carballojuanj attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT dalrerafael attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren
AT ayusocarmen attentiondeficithyperactivitydisordergeneticassociationstudyinacohortofspanishchildren