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General v. specific vulnerabilities: polygenic risk scores and higher-order psychopathology dimensions in the Adolescent Brain Cognitive Development (ABCD) Study

Published online by Cambridge University Press:  14 September 2021

Monika A. Waszczuk*
Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
Jiaju Miao
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Anna R. Docherty
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Andrey A. Shabalin
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA
Katherine G. Jonas
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Giorgia Michelini
Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA
Roman Kotov
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA
Author for correspondence: Monika A. Waszczuk, E-mail:



Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology.


The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS.


Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040–0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062).


PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.

Original Article
Copyright © The Author(s), 2021. Published by Cambridge University Press

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