A phenome-wide association study of cross-disorder genetic liability in youth genetically similar to individuals from European reference populations.
| Title: | A phenome-wide association study of cross-disorder genetic liability in youth genetically similar to individuals from European reference populations. |
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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.; 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.; 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.; 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: | Nature. Mental health [Nat Ment Health] 2024 Nov; Vol. 2 (11), pp. 1327-1341. Date of Electronic Publication: 2024 Oct 14. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Nature Country of Publication: England NLM ID: 9918486688806676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2731-6076 (Electronic) Linking ISSN: 27316076 NLM ISO Abbreviation: Nat Ment Health Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Springer Nature, [2023]- |
| 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 an exploratory phenome-wide association study (phenotype n=1,271-1,697) 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 DevelopmentSM (ABCD) Study. We found that Neurodevelopmental and Internalizing PRS were significantly associated with phenotypes across multiple domains (Neurodevelopmental: 190 and 214 (147 and 165 after pruning correlated phenotypes at an R2 of 0.6); Internalizing: 124 and 183 (93 and 131 after pruning) phenotypes at baseline and two-year follow-up, respectively), whereas Compulsive and Psychotic PRS showed zero and two significant associations, respectively, after Bonferroni correction. Compulsive, Psychotic, and Neurodevelopmental PRS were further associated with brain structure metrics, with minimal evidence that brain structure indirectly linked PRS to two-year follow-up outcomes. Genetic variation influencing risk to psychopathology manifests broadly as behaviors, psychopathology symptoms, and related risk factors in middle childhood and early adolescence. |
| Competing Interests: | Competing Interests Statement: The authors do not report any competing interests. |
| Grant Information: | F31 AA029934 United States AA NIAAA NIH HHS; R01 DA054750 United States DA NIDA NIH HHS |
| Contributed Indexing: | Keywords: Internalizing; Neurodevelopmental; Phenome-wide Association Study (PheWAS); polygenic risk scores |
| Entry Date(s): | Date Created: 20260316 Latest Revision: 20260318 |
| Update Code: | 20260318 |
| PubMed Central ID: | PMC12981648 |
| DOI: | 10.1038/s44220-024-00313-2 |
| PMID: | 41836634 |
| Database: | MEDLINE |
Journal Article