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Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function

Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function
Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function
Objectives. Motor coordination problems are frequent in children with attention deficit/hyperactivity disorder (ADHD). We performed a genome-wide association study to identify genes contributing to motor coordination problems, hypothesizing that the presence of such problems in children with ADHD may identify a sample of reduced genetic heterogeneity. Methods. Children with ADHD from the International Multicentre ADHD Genetic (IMAGE) study were evaluated with the Parental Account of Children's Symptoms. Genetic association testing was performed in PLINK on 890 probands with genome-wide genotyping data. Bioinformatics enrichment-analysis was performed on highly ranked findings. Further characterization of the findings was conducted in 313 Dutch IMAGE children using the Developmental Coordination Disorder Questionnaire (DCD-Q). Results. Although none of the findings reached genome-wide significance, bioinformatics analysis of the top-ranked findings revealed enrichment of genes for motor neuropathy and amyotrophic lateral sclerosis. Genes involved in neurite outgrowth and muscle function were also enriched. Among the highest ranked genes were MAP2K5, involved in restless legs syndrome, and CHD6, causing motor coordination problems in mice. Further characterization of these findings using DCD-Q subscales found nominal association for 15 SNPs. Conclusions. Our findings provide clues about the aetiology of motor coordination problems, but replication studies in independent samples are necessary.
motor coordination problems, adhd, genome-wide association study (gwas), neurite outgrowth, skeletal muscle function
1562-2975
Fliers, Ellen A.
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Vasquez, Alejandro Arias
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Poelmans, Geert
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Rommelse, Nanda
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Altink, Marieke
e2a0777f-0953-4454-8454-faea42dace10
Buschgens, Cathelijne
c7fe9bd5-b989-4fcf-af2e-0ad2f21c66be
Asherson, Philip
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Banaschewski, Tobias
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Ebstein, Richard
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Gill, Michael
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Miranda, Ana
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Mulas, Fernando
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Oades, Robert D.
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Roeyers, Herbert
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Rothenberger, Aribert
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Sergeant, Joseph
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Sonuga-Barke, Edmund
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Steinhausen, Hans-Christoph
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Faraone, Stephen V.
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Buitelaar, Jan K.
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Franke, Barbara
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Fliers, Ellen A.
1d06448c-7179-419c-bf82-4fb84035ffe3
Vasquez, Alejandro Arias
4ac217e5-bd05-417e-8d7f-71d5b90446d3
Poelmans, Geert
80351746-1298-4dbb-b736-b955515dc4c7
Rommelse, Nanda
3b0bb74c-f8d0-4515-9e01-fd33ce82fef1
Altink, Marieke
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Buschgens, Cathelijne
c7fe9bd5-b989-4fcf-af2e-0ad2f21c66be
Asherson, Philip
a734c1f6-f31a-450b-81c3-ba7bb373e147
Banaschewski, Tobias
4627c589-04cc-4f5b-ac2d-05f547f63dfd
Ebstein, Richard
61f78327-53b0-453d-8b2a-1a5363ebff67
Gill, Michael
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Miranda, Ana
e416878c-5ff3-4892-bb8f-17e8de0884ac
Mulas, Fernando
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Oades, Robert D.
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Roeyers, Herbert
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Rothenberger, Aribert
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Sergeant, Joseph
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Sonuga-Barke, Edmund
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Steinhausen, Hans-Christoph
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Faraone, Stephen V.
bd307516-e8db-4d38-b649-9d7d7caafe93
Buitelaar, Jan K.
a2e08a14-4de4-419e-9ea8-1e97ebbdddba
Franke, Barbara
f71c8989-a108-40c4-a159-80a1e60b56bf

Fliers, Ellen A., Vasquez, Alejandro Arias, Poelmans, Geert, Rommelse, Nanda, Altink, Marieke, Buschgens, Cathelijne, Asherson, Philip, Banaschewski, Tobias, Ebstein, Richard, Gill, Michael, Miranda, Ana, Mulas, Fernando, Oades, Robert D., Roeyers, Herbert, Rothenberger, Aribert, Sergeant, Joseph, Sonuga-Barke, Edmund, Steinhausen, Hans-Christoph, Faraone, Stephen V., Buitelaar, Jan K. and Franke, Barbara (2011) Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function. The World Journal of Biological Psychiatry. (doi:10.3109/15622975.2011.560279). (PMID:21473668)

Record type: Article

Abstract

Objectives. Motor coordination problems are frequent in children with attention deficit/hyperactivity disorder (ADHD). We performed a genome-wide association study to identify genes contributing to motor coordination problems, hypothesizing that the presence of such problems in children with ADHD may identify a sample of reduced genetic heterogeneity. Methods. Children with ADHD from the International Multicentre ADHD Genetic (IMAGE) study were evaluated with the Parental Account of Children's Symptoms. Genetic association testing was performed in PLINK on 890 probands with genome-wide genotyping data. Bioinformatics enrichment-analysis was performed on highly ranked findings. Further characterization of the findings was conducted in 313 Dutch IMAGE children using the Developmental Coordination Disorder Questionnaire (DCD-Q). Results. Although none of the findings reached genome-wide significance, bioinformatics analysis of the top-ranked findings revealed enrichment of genes for motor neuropathy and amyotrophic lateral sclerosis. Genes involved in neurite outgrowth and muscle function were also enriched. Among the highest ranked genes were MAP2K5, involved in restless legs syndrome, and CHD6, causing motor coordination problems in mice. Further characterization of these findings using DCD-Q subscales found nominal association for 15 SNPs. Conclusions. Our findings provide clues about the aetiology of motor coordination problems, but replication studies in independent samples are necessary.

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More information

Published date: 7 April 2011
Keywords: motor coordination problems, adhd, genome-wide association study (gwas), neurite outgrowth, skeletal muscle function
Organisations: Clinical Neuroscience

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Local EPrints ID: 194665
URI: https://eprints.soton.ac.uk/id/eprint/194665
ISSN: 1562-2975
PURE UUID: 54d5f365-8a3f-4d15-8855-ec9cecd6cd7c

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Date deposited: 09 Aug 2011 13:15
Last modified: 16 Jul 2019 23:25

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Contributors

Author: Ellen A. Fliers
Author: Alejandro Arias Vasquez
Author: Geert Poelmans
Author: Nanda Rommelse
Author: Marieke Altink
Author: Cathelijne Buschgens
Author: Philip Asherson
Author: Tobias Banaschewski
Author: Richard Ebstein
Author: Michael Gill
Author: Ana Miranda
Author: Fernando Mulas
Author: Robert D. Oades
Author: Herbert Roeyers
Author: Aribert Rothenberger
Author: Joseph Sergeant
Author: Edmund Sonuga-Barke
Author: Hans-Christoph Steinhausen
Author: Stephen V. Faraone
Author: Jan K. Buitelaar
Author: Barbara Franke

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