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High loading of polygenic risk for ADHD in children with comorbid aggression

(2013) AMERICAN JOURNAL OF PSYCHIATRY. 170(8). p.909-916
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Organization
Abstract
Objective: Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. Method: Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. Results: Polygenic risk for ADD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by,the aggression items. Conclusions: Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.
Keywords
DE-NOVO MUTATIONS, GENOME-WIDE ASSOCIATION, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, DEFICIT-HYPERACTIVITY-DISORDER, SYMPTOMS, AUTISM, GENETIC-BASIS, OPPOSITIONAL DEFIANT, CONDUCT DISORDER, ANTISOCIAL-BEHAVIOR

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Citation

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Chicago
Hamshere, ML, K Langley, J Martin, SS Agha, E Stergiakouli, RJL Anney, J Buitelaar, et al. 2013. “High Loading of Polygenic Risk for ADHD in Children with Comorbid Aggression.” American Journal of Psychiatry 170 (8): 909–916.
APA
Hamshere, M., Langley, K., Martin, J., Agha, S., Stergiakouli, E., Anney, R., Buitelaar, J., et al. (2013). High loading of polygenic risk for ADHD in children with comorbid aggression. AMERICAN JOURNAL OF PSYCHIATRY, 170(8), 909–916.
Vancouver
1.
Hamshere M, Langley K, Martin J, Agha S, Stergiakouli E, Anney R, et al. High loading of polygenic risk for ADHD in children with comorbid aggression. AMERICAN JOURNAL OF PSYCHIATRY. AMER PSYCHIATRIC PUBLISHING, INC; 2013;170(8):909–16.
MLA
Hamshere, ML, K Langley, J Martin, et al. “High Loading of Polygenic Risk for ADHD in Children with Comorbid Aggression.” AMERICAN JOURNAL OF PSYCHIATRY 170.8 (2013): 909–916. Print.
@article{4334234,
  abstract     = {Objective: Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder.
Method: Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression.
Results: Polygenic risk for ADD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by,the aggression items.
Conclusions: Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.},
  author       = {Hamshere, ML and Langley, K and Martin, J and Agha, SS and Stergiakouli, E and Anney, RJL and Buitelaar, J and Faraone, SV and Lesch, KP and Neale, BM and Franke, B and Barke, Edmund and Asherson, P and Merwood, A and Kuntsi, J and Medland, SE and Ripke, S and Steinhausen, HC and Freitag, C and Reif, A and Renner, TJ and Romanos, M and Romanos, J and Warnke, A and Meyer, J and Palmason, H and Vasquez, AA and Lambregts-Rommelse, N and Roeyers, Herbert and Biederman, J and Doyle, AE and Hakonarson, H and Rothenberger, A and Banaschewski, T and Oades, RD and McGough, JJ and Kent, L and Williams, N and Owen, MJ and Holmans, P and O'Donovan, MC and Thapar, A},
  issn         = {0002-953X},
  journal      = {AMERICAN JOURNAL OF PSYCHIATRY},
  language     = {eng},
  number       = {8},
  pages        = {909--916},
  publisher    = {AMER PSYCHIATRIC PUBLISHING, INC},
  title        = {High loading of polygenic risk for ADHD in children with comorbid aggression},
  volume       = {170},
  year         = {2013},
}

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