Active · Iteration 1 published
Mapping Schizophrenia Risk
Can schizophrenia's hundreds of risk loci be resolved into targetable biology?
- Why it matters
- Two decades of GWAS have identified hundreds of schizophrenia risk loci, but translating those associations into mechanisms remains a central bottleneck. This iteration tests cell-type, regulatory, evolutionary-constraint, cross-disorder, and drug-target convergence using public genetic and annotation data. No original experimental data were generated.
- Iteration 1 findings
- Schizophrenia genetic risk converges on constrained synaptic genes in neuronsAcross five genetic analyses, schizophrenia common-variant risk maps to neuronal synaptic programs; the tested microglial marker analysis was not enriched. Within the broadly constrained synaptic class, SCZ-associated genes show additional constraint concentration (within-class OR=6.94, p=0.004). EGR1 and MEF2C motifs are enriched near SCZ gene promoters but are shared across neurodevelopmental disorders. CTCF is the only tested factor showing possibly SCZ-preferential motif enrichment. Drug-target overlap depends on the comparison universe. These are computational findings from public data and annotation resources.