A cross-disease, pleiotropy-driven approach for therapeutic target prioritization and evaluation.
Cell Rep Methods
; 4(4): 100757, 2024 Apr 22.
Article
in En
| MEDLINE
| ID: mdl-38631345
ABSTRACT
Cross-disease genome-wide association studies (GWASs) unveil pleiotropic loci, mostly situated within the non-coding genome, each of which exerts pleiotropic effects across multiple diseases. However, the challenge "W-H-W" (namely, whether, how, and in which specific diseases pleiotropy can inform clinical therapeutics) calls for effective and integrative approaches and tools. We here introduce a pleiotropy-driven approach specifically designed for therapeutic target prioritization and evaluation from cross-disease GWAS summary data, with its validity demonstrated through applications to two systems of disorders (neuropsychiatric and inflammatory). We illustrate its improved performance in recovering clinical proof-of-concept therapeutic targets. Importantly, it identifies specific diseases where pleiotropy informs clinical therapeutics. Furthermore, we illustrate its versatility in accomplishing advanced tasks, including pathway crosstalk identification and downstream crosstalk-based analyses. To conclude, our integrated solution helps bridge the gap between pleiotropy studies and therapeutics discovery.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genome-Wide Association Study
/
Genetic Pleiotropy
Limits:
Humans
Language:
En
Journal:
Cell Rep Methods
Year:
2024
Document type:
Article
Affiliation country:
China