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

Hamshere, Marian Lindsay, Langley, Kate, Martin, Joanna, Agha, Sharifah Shameem, Stergiakouli, Evangelia, Anney, Richard, Buitelaar, Jan, Faraone, Stephen V., Lesch, Klaus-Peter, Neale, Benjamin M., Franke, Barbara, Sonuga-Barke, Edmund, Asherson, Philip, Merwood, Andrew, Kuntsi, Jonna, Medland, Sarah E., Ripke, Stephan, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J., Romanos, Marcel, Romanos, Jasmin, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Roeyers, Herbert, Biederman, Joseph, Doyle, Alysa E., Hakonarson, Hakon, Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D., McGough, James J., Kent, Lindsey, Williams, Nigel Melville, Owen, Michael John, Holmans, Peter Alan, O'Donovan, Michael Conlon and Thapar, Anita 2013. High loading of polygenic risk for ADHD in children with comorbid aggression. American Journal of Psychiatry 170 (8) , pp. 909-916. 10.1176/appi.ajp.2013.12081129

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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 ADHD, 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RJ Pediatrics
Publisher: American Psychiatric Association
ISSN: 0002-953X
Funders: Wellcome Trust, MRC, Action Research
Last Modified: 16 May 2019 22:30
URI: http://orca.cf.ac.uk/id/eprint/58159

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