Single-cell multi-cohort dissection of the schizophrenia transcriptome
Broad Institute · Harvard University · +5 more institutions
Abstract
The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation and the development of more effective therapies. Here, we performed single-cell dissection of schizophrenia-associated transcriptomic changes in the human prefrontal cortex across 140 individuals in two independent cohorts. Excitatory neurons were the most affected cell group, with transcriptional changes converging on neurodevelopment and synapse-related molecular pathways. Transcriptional alterations included known genetic risk factors, suggesting convergence of rare and common genomic variants on neuronal population-specific alterations in schizophrenia. Based on the magnitude of schizophrenia-associated transcriptional…
Citation impact
- FWCI
- 26.01
- Percentile
- 100%
- References
- 96
Authors
216- WBW. Brad RuzickaCorresponding
Broad Institute, Harvard University, McLean Hospital
- SMShahin MohammadiCorresponding
Broad Institute, Massachusetts Institute of Technology
- JFJohn F. FullardCorresponding
Icahn School of Medicine at Mount Sinai
- JDJosé Dávila-VelderrainCorresponding
Broad Institute, Human Technopole, Massachusetts Institute of Technology
- SSSivan Subburaju
Harvard University, McLean Hospital
Topics & keywords
- Transcriptome
- Schizophrenia (object-oriented programming)
- Biology
- Neuroscience
- Prefrontal cortex
- Population
- Cytoarchitecture
- Genetics
Funding
- UDU.S. Department of Veterans AffairsAward: BX002395
- NINational Institutes of HealthAwards: R01MH125516, K08MH122911, R01MH110921, R01AG062335, R01MH109715, R01MH110927, U01MH116492, R01MH126459, U01MH116442, R01MH109978, R01MH105898, R01MH121521, U01MH103340, R01MH109677, R01MH110920, R21MH105853, U01MH122591, U01MH122849, U01MH116441, U01MH103392, U01MH116489, R01MH117406, R01AG050986, HHSN271201300031C, R01AG067025, R01MH125246