Topic: Brain proteins, microglia and lab models
We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein-coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European American and one African American, increasing overlap, reproducibility and consistency of findings from single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Finally, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics. It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ayalew, M., Le-Niculescu, H., Levey, D. F., Jain, N., Changala, B., Patel, S. D., et al. (2012). Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Molecular psychiatry. https://doi.org/10.1038/mp.2012.37
Vancouver
Ayalew M, Le-Niculescu H, Levey DF, Jain N, Changala B, Patel SD, et al. Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Molecular psychiatry. 2012. doi:10.1038/mp.2012.37. PMID: 22584867.
BibTeX
@article{ayalew2012-22584867,
author = {Ayalew, M. and Le-Niculescu, H. and Levey, D. F. and Jain, N. and Changala, B. and Patel, S. D. and Winiger, E. and Breier, A. and others},
title = {{Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction}},
journal = {Molecular psychiatry},
year = {2012},
doi = {10.1038/mp.2012.37},
pmid = {22584867},
url = {https://doi.org/10.1038/mp.2012.37}
}
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Key findings
- Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability.
- Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics.
- It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.
Why it matters
This study used a convergent functional genomics approach to identify and prioritize genes involved in schizophrenia and to generate a genetic risk prediction score. It concerns schizophrenia, not Alzheimer disease, and provides no information about treating, curing, or preventing Alzheimer disease.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 397 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.8 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 5 / 6 | Cited 35.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 33 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Alexander B. Niculescu: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22584867) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
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