The University of Southampton
University of Southampton Institutional Repository

Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD

Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD
Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD
OBJECTIVE: Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD.

METHOD: The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales.

RESULTS: Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms (pempirical = .007) but not with inattentive symptoms (pempirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result (pempirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, pempirical = .0004; serotonin, pempirical = .0149; neuritic outgrowth, pempirical = .0452).

CONCLUSION: The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to identify biological risk factors involved in this disorder.
0890-8567
1204-1212
Bralten, Janita
58846276-bef7-4e45-891f-5f11639bc72d
Franke, Barbara
f71c8989-a108-40c4-a159-80a1e60b56bf
Waldman, Irwin
f1462246-bf96-44d7-bba3-18e1caebad37
Rommelse, Nanda
3b0bb74c-f8d0-4515-9e01-fd33ce82fef1
Hartman, Catharina
da019f4c-3e69-4071-9852-232bcc0f12ba
Asherson, Philip
a734c1f6-f31a-450b-81c3-ba7bb373e147
Banaschewski, Tobias
4627c589-04cc-4f5b-ac2d-05f547f63dfd
Ebstein, Richard P.
b7b70774-d400-4f33-84bf-11a21bc83170
Gill, Michael
408d1dfa-5205-4e50-8130-7b26aa8288e8
Miranda, Ana
e416878c-5ff3-4892-bb8f-17e8de0884ac
Oades, Robert D.
85d7ca21-1a76-458d-a3e3-69d4b13232db
Roeyers, Herbert
3554b6b3-e364-4a6a-9e8b-64f5188a6d60
Rothenberger, Aribert
736981ca-a16d-44b3-8312-2067dc792a6d
Sergeant, Joseph A.
fca17df1-498d-4009-b445-dc6033711ab0
Oosterlaan, Jaap
c255de5f-9d6e-4f57-af6c-b826a3b35324
Sonuga-Barke, Edmund
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Steinhausen, Hans-Christoph
991ad7f9-c5d1-4c61-8118-3d4895d2706d
Faraone, Stephen V.
bd307516-e8db-4d38-b649-9d7d7caafe93
Buitelaar, Jan K.
a2e08a14-4de4-419e-9ea8-1e97ebbdddba
Arias-Vásquez, Alejandro
5ed767eb-ca5e-49d8-8535-3a2f95fcf396
Bralten, Janita
58846276-bef7-4e45-891f-5f11639bc72d
Franke, Barbara
f71c8989-a108-40c4-a159-80a1e60b56bf
Waldman, Irwin
f1462246-bf96-44d7-bba3-18e1caebad37
Rommelse, Nanda
3b0bb74c-f8d0-4515-9e01-fd33ce82fef1
Hartman, Catharina
da019f4c-3e69-4071-9852-232bcc0f12ba
Asherson, Philip
a734c1f6-f31a-450b-81c3-ba7bb373e147
Banaschewski, Tobias
4627c589-04cc-4f5b-ac2d-05f547f63dfd
Ebstein, Richard P.
b7b70774-d400-4f33-84bf-11a21bc83170
Gill, Michael
408d1dfa-5205-4e50-8130-7b26aa8288e8
Miranda, Ana
e416878c-5ff3-4892-bb8f-17e8de0884ac
Oades, Robert D.
85d7ca21-1a76-458d-a3e3-69d4b13232db
Roeyers, Herbert
3554b6b3-e364-4a6a-9e8b-64f5188a6d60
Rothenberger, Aribert
736981ca-a16d-44b3-8312-2067dc792a6d
Sergeant, Joseph A.
fca17df1-498d-4009-b445-dc6033711ab0
Oosterlaan, Jaap
c255de5f-9d6e-4f57-af6c-b826a3b35324
Sonuga-Barke, Edmund
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Steinhausen, Hans-Christoph
991ad7f9-c5d1-4c61-8118-3d4895d2706d
Faraone, Stephen V.
bd307516-e8db-4d38-b649-9d7d7caafe93
Buitelaar, Jan K.
a2e08a14-4de4-419e-9ea8-1e97ebbdddba
Arias-Vásquez, Alejandro
5ed767eb-ca5e-49d8-8535-3a2f95fcf396

Bralten, Janita, Franke, Barbara, Waldman, Irwin, Rommelse, Nanda, Hartman, Catharina, Asherson, Philip, Banaschewski, Tobias, Ebstein, Richard P., Gill, Michael, Miranda, Ana, Oades, Robert D., Roeyers, Herbert, Rothenberger, Aribert, Sergeant, Joseph A., Oosterlaan, Jaap, Sonuga-Barke, Edmund, Steinhausen, Hans-Christoph, Faraone, Stephen V., Buitelaar, Jan K. and Arias-Vásquez, Alejandro (2013) Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 52 (11), 1204-1212. (doi:10.1016/j.jaac.2013.08.020). (PMID:24157394)

Record type: Article

Abstract

OBJECTIVE: Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD.

METHOD: The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales.

RESULTS: Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms (pempirical = .007) but not with inattentive symptoms (pempirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result (pempirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, pempirical = .0004; serotonin, pempirical = .0149; neuritic outgrowth, pempirical = .0452).

CONCLUSION: The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to identify biological risk factors involved in this disorder.

Full text not available from this repository.

More information

Published date: November 2013
Organisations: Clinical Neuroscience

Identifiers

Local EPrints ID: 360210
URI: https://eprints.soton.ac.uk/id/eprint/360210
ISSN: 0890-8567
PURE UUID: 5dafec89-12d9-4156-bc27-5e6bf1264e8a

Catalogue record

Date deposited: 29 Nov 2013 13:42
Last modified: 16 Jul 2019 21:16

Export record

Altmetrics

Contributors

Author: Janita Bralten
Author: Barbara Franke
Author: Irwin Waldman
Author: Nanda Rommelse
Author: Catharina Hartman
Author: Philip Asherson
Author: Tobias Banaschewski
Author: Richard P. Ebstein
Author: Michael Gill
Author: Ana Miranda
Author: Robert D. Oades
Author: Herbert Roeyers
Author: Aribert Rothenberger
Author: Joseph A. Sergeant
Author: Jaap Oosterlaan
Author: Edmund Sonuga-Barke
Author: Hans-Christoph Steinhausen
Author: Stephen V. Faraone
Author: Jan K. Buitelaar
Author: Alejandro Arias-Vásquez

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×