Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline.

Area of Science:

• Genetics and Immunology
• Pharmacology and Drug Discovery

Background:

• Genome-wide association studies (GWAS) have identified numerous genes for psoriasis and psoriatic arthritis (PsA).
• However, a limited number of these identified genes have been translated into therapeutic targets for these conditions.

Purpose of the Study:

• To identify and analyze potential therapeutic targets for psoriasis and psoriatic arthritis (PsA).
• Utilized the Priority Index (Pi) approach, a genetics-dependent method for prioritizing drug targets.

Main Methods:

• Annotated significant genetic variants from GWAS for psoriasis, PsA, and combined psoriatic disease.
• Applied the Pi pipeline, incorporating genomic and annotation predictors, pathway enrichment, and pathway crosstalk analysis.

Main Results:

• Identified several gene targets with biological relevance to psoriasis and PsA.
• Some targets are under investigation (e.g., ICAM1, TYK2), while others are novel (e.g., LNPEP, UBLCP1, YAP1).
• Discovered multiple nodal points for therapeutic intervention, including pathways like PI3K/AKT.

Conclusions:

• The Priority Index (Pi) successfully identified data-driven candidate therapeutic targets and pathways for psoriasis and PsA.
• This analysis is valuable for developing novel psoriatic therapies, especially given the limited PsA-specific research and targets.