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The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology

Brikell, Isabell, Larsson, Henrik, Lu, Yi, Pettersson, Erik, Chen, Qi, Kuja-Halkola, Ralf, Karlsson, Robert, Lahey, Benjamin B, Lichtenstein, Paul and Martin, Joanna 2018. The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology. Molecular Psychiatry 10.1038/s41380-018-0109-2

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Abstract

Common genetic risk variants have been implicated in the etiology of clinical ADHD diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric problems, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing and internalizing symptoms, using structural equation modelling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing and depressive symptoms (R2=0.26%-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading=0.50, range=0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~1% (p-value<0.0001) of the variance in the general psychopathology factor and ~0.50% (p-value<0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Nature Publishing Group
ISSN: 1359-4184
Date of First Compliant Deposit: 14 May 2018
Date of Acceptance: 14 May 2018
Last Modified: 04 Jun 2019 09:50
URI: http://orca-mwe.cf.ac.uk/id/eprint/111440

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