Functional Heritability Partitioning, Multi-Tissue Transcriptomic Colocalization, and Pharmacogenomic Target Deconvolution Across 127 Alzheimer's Disease Susceptibility Loci

Background: The landmark genome-wide association meta-analysis of Alzheimer's disease (AD) and AD-by-proxy across N = 2,815,127 individuals (Uffelmann et al., Nature, 2026) expanded the known susceptibility landscape to 127 independent genomic risk loci (160 association signals) and established an autosomal common-variant SNP heritability of h2_SNP = 16.0% on the liability scale. Translating these 127 static statistical signals into pathway-stratified clinical trials requires resolving three quantitative gaps: how the non-APOE polygenic architecture partitions across distinct cellular programs

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