Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias

GWAS meta-analysis (128,681 cases, 849,833 controls), 91 associated loci including 16 new, polygenic score excluding APOE

This GWAS meta-analysis of 128,681 cases (or proxies) and 849,833 controls of European ancestry identifies 91 loci associated with Alzheimer's disease and related dementias risk, including 16 new loci. A polygenic score combining all loci except APOE is primarily associated with clinically diagnosed Alzheimer's disease. Pleiotropy and genetic correlation analyses refine the relative contribution of inflammation (microglial pathway), lipid metabolism, and tau biology in dementia genetic architecture.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This landmark meta-analysis provides the most comprehensive polygenic mapping of dementias to date. Without direct individual diagnostic impact, it fuels future clinical polygenic score construction and opens therapeutic leads for the most represented biological pathways — particularly microglial and tau. Included here exceptionally (population-level GWAS) for its reach in the clinical genetics community.

Clinical impact: 1/3 · Evidence strength: 3/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 7/10