Mapping specific and cross disorder polygenic risk scores onto dimensional psychopathology at age 9-10: Baseline results from the ABCD Study

Dylan Hughes, BS

Massachusetts General Hospital
Mapping specific and cross disorder polygenic risk scores onto dimensional psychopathology at age 9-10: Baseline results from the ABCD Study

Scientific Abstract

Background: Genome wide association studies (GWAS) in psychiatry, and polygenic risk score (PRS) analyses, have focused primarily on disorders that emerge in adulthood and have enrolled adult participants. Effects of polygenic loading for these disorders on psychopathology in children remain largely unexplored. Dimensional measures of psychopathology in children may index risk for emergence of full-blown disorders later in life. As such, an understanding of how genetic loading for these disorders maps onto dimensional symptoms in children may have value for prognosis and early intervention. Leveraging baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, we examined how indices of polygenic risk track with dimensional psychopathology at age 9-10.

Methods: GWAS data from 4,413 non-related ABCD participants of European descent was used to estimate effects of 8 disorder-specific PRS, and both conventional and genomic structural equation modeling (GSEM)-derived (compulsive/perfectionistic, mood/psychotic, neurodevelopmental) cross-disorder PRS, on 12 dimensions of psychopathology, captured via parent-reported ratings.

Results: Among disorder-specific PRS scores, ADHD and MDD scores predicted diffuse psychopathology (9 phenotypes each; p’s .003 to 2.8E-09). Among GSEM cross-disorder factors, the neurodevelopmental factor most strongly predicted psychopathology, across the broadest range of categories (11 total dimensions; p’s .004 to 2.6E-09).

Conclusions: Genetic underpinnings of dimensional psychopathology at age 9-10 predominantly reflect those of neurodevelopmental disorders. Notably, effects of such genetic loading are clinically diffuse at age 9-10. Future ABCD studies, including with intermediate biological markers, may clarify not only how but when more parsimonious relationships between disease- specific PRS and specific emergent psychopathology arise during adolescence.

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research Areas

Authors

Dylan Hughes, BS, Casey Hopkinson, BS, Hamdi Eryilmaz, PhD, Alysa Doyle, PhD, Erin Dunn, ScD, MPH, Phil Lee, PhD, Joshua Roffman, MD

Principal Investigator

Joshua Roffman, MD