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• W4387476788 abstract "More than 50% of youth with ADHD exhibit clinically significant aggression, representing high comorbidity. Although this points to the common genetic risk variants for the etiology of ADHD and aggression in youth, studies are limited that examine the common genetic variation of ADHD and clinical high aggression, and their subtypes. The objectives of this study were to assess the genetic relationship between ADHD and clinical aggression in children. The study tested whether 1) ADHD polygenic risk scores (PRS) predicts aggression case-control status, 2) whether aggression PRS predicts ADHD symptoms, and 3) whether aggression PRS predicts ADHD symptoms differently in children with “likely ADHD diagnosis”. 1) 232 youth of European white ancestry were recruited as a part of an ongoing study of childhood clinical aggression in Toronto, Canada. The case status was based on the participant scoring > 90th %tile on aggression subscales of both the Child Behaviour Checklist (CBCL) and the Teacher Report Form, and a minimum two-year history of the behavior. 2) and 3) 3704 children (age: 9.9 +-0.6) of European ancestry were recruited as part of the Adolescent Brain Cognitive Development (ABCD) study. Continuous measures of attention problems and ADHD were obtained from the baseline CBCL scores. Based on the previous studies with CBCL and ABCD, the “likely ADHD diagnosis” group was defined as youth above >65 t-score on either attention or ADHD scales of the CBCL (n=256). Two PRSs were calculated using the standard clumping and thresholding methods with the p-value thresholds from 5 × 10-8 to 1 in PRSice2, controlling for sex, collection site (21 sites), and the first three principal components. Data for both PRSs came from the pediatric population of the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium (Ip, 2021; Middeldorp, 2016). Linear and logistic regressions were used to analyze the associations between aggression PRS and ADHD scores in the ABCD sample, and between ADHD PRS and aggression case/control status in the Toronto sample, respectively. ADHD PRS significantly explained ∼ 6% of the case-control status for the Toronto Child Aggression sample (p = 0.002). Aggression PRS significantly explained ∼ 0.2% of the variance in the Attention Syndrome sub-scale and ADHD DSM-5 scale scores of the ABCD sample (p = 0.004-0.007). Interestingly, for the “likely ADHD diagnosis” sub-group, aggression PRS significantly explained ∼ 3% of the variance in the Attention Syndrome sub-scale scores of the ABCD sample, an increase from the full group (p = 0.007). On the other hand, for the “likely no diagnosis” participants with < 65 t-score, the variance in attention problems explained by the aggression PRS decreased to ∼ 0.015% (p = 0.019). There were significant associations between ADHD PRS with aggression case status and aggression PRS with ADHD. Our preliminary results indicate evidence that clinical aggression and ADHD share common genetic factors based on both clinical and population youth samples. The genetic overlap between aggression and ADHD was stronger in children with likely ADHD diagnoses. The large size of the ABCD sample provides increased power. The results may lead to generating better prediction strategies, for example, aggression acting as a genetic biomarker for ADHD or its subtypes. Personalized treatment strategies based on the genetic risk score may help with early prevention efforts." @default.
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• W4387476788 date "2023-10-01" @default.
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• W4387476788 title "W59. ASSESSMENT OF POLYGENIC RISK SCORES OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER AND AGGRESSION IN YOUTH: RESULTS FROM A CLINICAL AGGRESSION SAMPLE AND THE ABCD STUDY" @default.
• W4387476788 doi "https://doi.org/10.1016/j.euroneuro.2023.08.247" @default.
• W4387476788 hasPublicationYear "2023" @default.
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