| name | tooluniverse-gwas-drug-discovery |
| description | Transform GWAS signals into drug targets and repurposing opportunities. Connects GWAS-significant loci to causal genes via fine-mapping/eQTL, then to druggable proteins via DGIdb/OpenTargets, then to existing drugs via ChEMBL. Use for GWAS-to-target hypothesis generation, druggable-fraction analysis of disease loci, and human-genetics-validated drug-repurposing prioritization. |
| disable-model-invocation | true |
GWAS-to-Drug Target Discovery
Transform genome-wide association studies (GWAS) into actionable drug targets and repurposing opportunities.
IMPORTANT: Always use English terms in tool calls. Respond in the user's language.
Overview
This skill bridges genetic discoveries from GWAS with drug development by:
- Identifying genetic risk factors - Finding genes associated with diseases
- Assessing druggability - Evaluating which genes can be targeted by drugs
- Prioritizing targets - Ranking candidates by genetic evidence strength
- Finding existing drugs - Discovering approved/investigational compounds
- Identifying repurposing opportunities - Matching drugs to new indications
Key insight: Targets with genetic support have 2x higher probability of clinical approval (Nelson et al., Nature Genetics 2015).
Reasoning Strategy
GWAS-to-drug translation succeeds when you think causally. A genetic association provides causal direction that observational data cannot: if a loss-of-function variant protects against disease, an inhibitor of that gene's product is the hypothesis to test. The direction of effect (LOF vs. GOF) determines whether you need an inhibitor or an agonist — get this wrong and the drug works backwards. GWAS effect sizes are small (odds ratios of 1.1–1.5 are typical), but the drug effect may be much larger or smaller than the genetic effect; the genetic signal validates the target, not the dose. Always integrate multiple lines of evidence (eQTL colocalization, pQTL, L2G score) before committing to a target, because many GWAS variants tag the causal gene only indirectly.
