Penalized Regression Based Proteome-Wide Association Study Reveals Potential Population-Specific Drug Targets for Alzheimer's Disease in European and African American Cohorts.

Alzheimer's disease (AD) is a complex neurodegenerative disorder with significant genetic underpinnings, yet effective treatments remain elusive. To bridge the gap between genetic discoveries and therapeutic development, we conducted a penalized regression based proteome-wide association study (PWAS) in both European and African American populations. Using publicly available GWAS summary statistics and the BLISS model, we identified 37 protein-coding genes significantly associated with AD risk, including APOE and BCAM in both populations. We further applied the GREP model to prioritize repositionable drugs targeting these genes, identifying 30 significant disease-target-drug pairs. Notably, Ramipril and BAY 85-8501 emerged as top candidates for AD treatment in European and African American populations, respectively. These findings highlight ancestry-specific drug targets, demonstrating the importance of diverse genetic studies in AD research and providing novel avenues for therapeutic intervention.