Advanced search
1 file | 477.12 KB

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

Author
Organization
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 (p(empirical) = .007) but not with inattentive symptoms (p(empirical) = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result (P-empirical = .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, p(empirical) = .0004; serotonin,. P-empirical = .0149; neuritic outgrowth, p(empirical) = .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.
Keywords
neurotransmitter systems, LARGE MULTICENTER ADHD, NITRIC-OXIDE SYNTHASE, IDENTIFIES ASSOCIATION, QUANTITATIVE TRAITS, DIAGNOSTIC-APPROACH, CRITERION VALIDITY, METAANALYSIS, DOPAMINE, attention-deficit/hyperactivity disorder symptoms, genetic pathways, neuritic outgrowth, GENOME-WIDE ASSOCIATION, DEFICIT HYPERACTIVITY DISORDER

Downloads

  • Bralten Franke2013 JAACAP.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 477.12 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Bralten, J, B Franke, I Waldman, N Rommelse, C Hartman, P Asherson, T Banaschewski, et al. 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.
APA
Bralten, J., Franke, B., Waldman, I., Rommelse, N., Hartman, C., Asherson, P., Banaschewski, T., et al. (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.
Vancouver
1.
Bralten J, Franke B, Waldman I, Rommelse N, Hartman C, Asherson P, et al. 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. 2013;52(11):1204–12.
MLA
Bralten, J, B Franke, I Waldman, et al. “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 (2013): 1204–1212. Print.
@article{4333797,
  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 (p(empirical) = .007) but not with inattentive symptoms (p(empirical) = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result (P-empirical = .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, p(empirical) = .0004; serotonin,. P-empirical = .0149; neuritic outgrowth, p(empirical) = .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.},
  author       = {Bralten, J and Franke, B and Waldman, I and Rommelse, N and Hartman, C and Asherson, P and Banaschewski, T and Ebstein, RP and Gill, M and Miranda, A and Oades, RD and Roeyers, Herbert and Rothenberger, A and Sergeant, JA and Oosterlaan, J and Barke, Edmund and Steinhausen, HC and Faraone, SV and Buitelaar, JK and Arias-Vasquez, A},
  issn         = {0890-8567},
  journal      = {JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY},
  language     = {eng},
  number       = {11},
  pages        = {1204--1212},
  title        = {Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD},
  url          = {http://dx.doi.org/10.1016/j.jaac.2013.08.020},
  volume       = {52},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: