| Autor: |
Forsyth JK, Zhu J, Chavannes AS, Trevorrow ZH, Hyat M, Sievertsen SA, Ferreira-Ianone S, Conomos MP, Nuechterlein KH, Asarnow RF, Green MF, Karlsgodt KH, Perkins DO, Cannon TD, Addington JM, Cadenhead KS, Cornblatt BA, Keshavan MS, Mathalon DH, Stone WS, Tsuang MT, Walker EF, Woods SW, Narr KL, McEwen SC, Schleifer CH, Yee CM, Diehl CK, Guha A, Miller GA, Alexander-Bloch AF, Seidlitz J, Bethlehem RAI, Ophoff RA, Bearden CE |
| Jazyk: |
angličtina |
| Zdroj: |
MedRxiv : the preprint server for health sciences [medRxiv] 2024 Aug 06. Date of Electronic Publication: 2024 Aug 06. |
| DOI: |
10.1101/2024.08.02.24311302 |
| Abstrakt: |
Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals. CNV associations were assessed for replication in 235 SSD relatives and 583 controls, and 9,930 youth from the Adolescent Brain Cognitive Development (ABCD) Study. Known SSD- and neurodevelopmental disorder (NDD)-risk CNVs were associated with borderline intellectual functioning in SSD cases (odds ratios (OR) = 7.09 and 4.57, respectively); NDD-risk deletions were nominally associated with childhood-onset psychosis (OR = 4.34). Furthermore, deletion of genes involved in regulating gene expression during fetal brain development was associated with borderline intellectual functioning across SSD cases and non-cases (OR = 2.58), with partial replication in the ABCD cohort. Exploratory analyses of cortical morphology showed associations between fetal gene regulatory gene deletions and altered gray matter volume and cortical thickness across cohorts. Results highlight contributions of known risk CNVs to phenotypic variability in SSD and the utility of a neurodevelopmental framework for identifying mechanisms that influence phenotypic variability in SSDs, as well as the broader population, with implications for personalized medicine approaches to care. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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