Polygenic Risk, Psychopathology, and Personalized Functional Brain Network Topography in Adolescence Article Swipe
Kevin Sun
,
J. Eric Schmitt
,
Tyler M. Moore
,
Ran Barzilay
,
Laura Almasy
,
Laura M. Schultz
,
Allyson P. Mackey
,
Eren Kafadar
,
Zhiqiang Sha
,
Jakob Seidlitz
,
Travis T. Mallard
,
Zaixu Cui
,
Hongming Li
,
Yong Fan
,
Damien A. Fair
,
Theodore D. Satterthwaite
,
Arielle S. Keller
,
Aaron Alexander‐Bloch
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.09.20.24314007
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.09.20.24314007
Importance Functional brain networks are associated with both behavior and genetic factors. To uncover biological mechanisms of psychopathology, it is critical to define how the spatial organization of these networks relates to genetic risk during development. Objective To determine the relationships among transdiagnostic polygenic risk scores (PRSs), personalized functional brain networks (PFNs), and overall psychopathology (p-factor) during early adolescence. Design The Adolescent Brain Cognitive Development (ABCD) Study lll is an ongoing longitudinal cohort study of 21 collection sites across the United States. Here, we conduct a cross-sectional analysis of ABCD baseline data, collected 2017-2018. Setting The ABCD Study ® is a multi-site community-based study. Participants The sample is largely recruited through school systems. Exclusion criteria included severe sensory, intellectual, medical, or neurological issues that interfere with protocol and scanner contraindications. Split-half subsets were used for cross-validation, matched on age, ethnicity, family structure, handedness, parental education, site, sex, and anesthesia exposure. Exposures Polygenic risk scores of transdiagnostic genetic factors F1 (PRS-F1) and F2 (PRS-F2) derived from adults in Psychiatric Genomic Consortium and UK Biobanks datasets. PRS-F1 indexes liability for common psychiatric symptoms and disorders related to mood disturbance; PRS-F2 indexes liability for rarer forms of mental illness characterized by mania and psychosis. Main Outcomes and Measures (1) P-factor derived from bifactor models of youth-and parent-reported mental health assessments. (2) Person-specific functional brain network topography derived from functional magnetic resonance imaging (fMRI) scans. Results Total participants included 11,873 youths ages 9-10 years old; 5,678 (47.8%) were female, and the mean (SD) age was 9.92 (0.62) years. PFN topography was found to be heritable ( N =7,459, 57.1% of vertices h 2 p FDR <0.05, mean h 2 =0.35). PRS-F1 was associated with p-factor ( N =5,815, r =0.12, 95% CI [0.09–0.15], p<0.001). Interindividual differences in functional network topography were associated with p-factor ( N =7,459, mean r =0.12), PRS-F1 ( N =3,982, mean r =0.05), and PRS-F2 ( N =3,982, mean r =0.08). Cortical maps of p-factor and PRS-F1 regression coefficients were highly correlated ( r =0.7, p =0.003). Conclusions and Relevance Polygenic risk for transdiagnostic adulthood psychopathology is associated with both p-factor and heritable PFN topography during early adolescence. These results advance our understanding of the developmental drivers of psychopathology. Key Points Question What are the relationships among transdiagnostic polygenic risk scores (PRSs), personalized functional brain networks (PFNs), and overall psychopathology (p-factor) during early adolescence? Findings In this cross-sectional analysis of the Adolescent Brain Cognitive Development (ABCD) Study lll ( N =11,873, ages 9-10), we found that a PRS of common mood-related psychopathology in adulthood (PRS-F1) was associated with p-factor during early adolescence. Interindividual differences in p-factor, PRS-F1, and PRS-F2 (capturing more severe psychotic disorders in adulthood) were all robustly associated with PFN topography. Meaning Polygenic risk for transdiagnostic adulthood psychopathology is associated with both p-factor and PFN topography during early adolescence.
Related Topics
Concepts
Polygenic risk score
Psychopathology
Functional connectivity
Psychology
Neuroscience
Cognitive psychology
Biology
Clinical psychology
Genetics
Gene
Single-nucleotide polymorphism
Genotype
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.09.20.24314007
- OA Status
- green
- Cited By
- 3
- References
- 78
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4402858982
All OpenAlex metadata
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https://openalex.org/W4402858982Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.09.20.24314007Digital Object Identifier
- Title
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Polygenic Risk, Psychopathology, and Personalized Functional Brain Network Topography in AdolescenceWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
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2024Year of publication
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2024-09-26Full publication date if available
- Authors
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Kevin Sun, J. Eric Schmitt, Tyler M. Moore, Ran Barzilay, Laura Almasy, Laura M. Schultz, Allyson P. Mackey, Eren Kafadar, Zhiqiang Sha, Jakob Seidlitz, Travis T. Mallard, Zaixu Cui, Hongming Li, Yong Fan, Damien A. Fair, Theodore D. Satterthwaite, Arielle S. Keller, Aaron Alexander‐BlochList of authors in order
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https://doi.org/10.1101/2024.09.20.24314007Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.ncbi.nlm.nih.gov/pmc/articles/11469391Direct OA link when available
- Concepts
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Polygenic risk score, Psychopathology, Functional connectivity, Psychology, Neuroscience, Cognitive psychology, Biology, Clinical psychology, Genetics, Gene, Single-nucleotide polymorphism, GenotypeTop concepts (fields/topics) attached by OpenAlex
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3Total citation count in OpenAlex
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2025: 2, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.=3,982, | 310, 318 |
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