Alzheimer's disease target and drug discovery by leveraging multiomics and electronic health data.

Mendelian randomization and multiomics analyses identified 19 druggable targets for Alzheimer's disease, including protective variants in EPHX2, in individuals of European and African ancestry.

• Why it matters: Translating extensive genomic data into effective treatments for Alzheimer's disease remains challenging, highlighting the need for new target identification and validation methods.
• What they did: Researchers used Mendelian randomization on GWAS and multiomics datasets to nominate targets, validated the protective role of EPHX2 p.Arg287Gln through experiments, and analyzed electronic health records from 111,680 patients to find drugs linked to reduced AD incidence.
• The result: The findings suggest new therapeutic approaches for AD, with pharmacological inhibition of EPHX2 improving cognition in mice and drugs like trazodone and baclofen associated with lower AD risk in patients.