Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry.
| Title: | Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry. |
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| Authors: | Paul SE; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Colbert SMC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.; Gorelik AJ; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Hansen IS; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Nagella I; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Blaydon L; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Hornstein A; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Johnson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.; Hatoum AS; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.; Baranger DAA; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Elsayed NM; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Barch DM; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.; Department of Radiology, Washington University School of Medicine, St. Louis, MO.; Bogdan R; Department of Psychological and Brain Sciences, Washington University, St. Louis, MO.; Karcher NR; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO. |
| Source: | MedRxiv : the preprint server for health sciences [medRxiv] 2023 Feb 14. Date of Electronic Publication: 2023 Feb 14. |
| Publication Type: | Preprint; Journal Article |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Etiologic insights into psychopathology may be gained by using hypothesis-free methods to identify associations between genetic risk for broad psychopathology and phenotypes measured during adolescence, including both markers of child psychopathology and intermediate phenotypes such as neural structure that may link genetic risk with outcomes. We conducted a phenome-wide association study (phenotype n=1,269-1,694) of polygenic risk scores (PRS) for broad spectrum psychopathology (i.e., Compulsive, Psychotic, Neurodevelopmental, and Internalizing) in youth of PCA-selected European ancestry (n=5,556; ages 9-13) who completed the baseline and/or two-year follow-up of the ongoing Adolescent Brain Cognitive Development℠ (ABCD) Study. We found that Neurodevelopmental and Internalizing PRS were significantly associated with a host of proximal as well as distal phenotypes (Neurodevelopmental: 187 and 211; Internalizing: 122 and 173 phenotypes at baseline and two-year follow-up, respectively), whereas Compulsive and Psychotic PRS showed zero and one significant associations, respectively, after Bonferroni correction. Neurodevelopmental PRS were further associated with brain structure metrics (e.g., total volume, mean right hemisphere cortical thickness), with only cortical volume indirectly linking Neurodevelopmental PRS to grades in school. Genetic variation influencing risk to psychopathology manifests broadly as behaviors, psychopathology symptoms, and related risk factors in middle childhood and early adolescence. |
| Competing Interests: | Conflicts of interest: The authors do not report any conflicts of interest. |
| Grant Information: | U24 DA041147 United States DA NIDA NIH HHS; R01 AG061162 United States AG NIA NIH HHS; U01 DA041120 United States DA NIDA NIH HHS; R21 AA027827 United States AA NIAAA NIH HHS; U01 DA055367 United States DA NIDA NIH HHS; U24 DA041123 United States DA NIDA NIH HHS; F31 AA029934 United States AA NIAAA NIH HHS; K01 DA051759 United States DA NIDA NIH HHS; K01 AA030083 United States AA NIAAA NIH HHS; U01 DA041025 United States DA NIDA NIH HHS; U01 DA041089 United States DA NIDA NIH HHS; U01 DA041106 United States DA NIDA NIH HHS; U01 DA041148 United States DA NIDA NIH HHS; R01 MH113883 United States MH NIMH NIH HHS; R01 DA046224 United States DA NIDA NIH HHS; U01 DA041174 United States DA NIDA NIH HHS; R01 DA054750 United States DA NIDA NIH HHS; R01 MH090786 United States MH NIMH NIH HHS; U01 DA041093 United States DA NIDA NIH HHS; U01 MH109589 United States MH NIMH NIH HHS; U01 DA041134 United States DA NIDA NIH HHS; U01 DA041022 United States DA NIDA NIH HHS; R01 MH066031 United States MH NIMH NIH HHS; U01 DA041156 United States DA NIDA NIH HHS; U01 DA041117 United States DA NIDA NIH HHS; R01 AG045231 United States AG NIA NIH HHS; U01 DA041028 United States DA NIDA NIH HHS; U01 DA041048 United States DA NIDA NIH HHS |
| Contributed Indexing: | Keywords: Internalizing; Neurodevelopmental; Phenome-wide Association Study (PheWAS); polygenic risk scores |
| Entry Date(s): | Date Created: 20230224 Latest Revision: 20240923 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9949197 |
| DOI: | 10.1101/2023.02.10.23285783 |
| PMID: | 36824847 |
| Database: | MEDLINE |
Preprint; Journal Article