ArticleHuman genomics2026
Progranulin genetic variant rs5848 displays ancestry-specific associations with Alzheimer's disease.
Article in Human genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundProgranulin is a molecular modifier of Alzheimer’s disease (AD). However, its cis-regulatory region remains under-characterized. Association studies of genetic variants in this region with AD have obtained conflicting results across different human populations.
methodsWe define the cis-regulatory region of the progranulin gene (GRN). Querying the genetically admixed Alzheimer’s Disease Sequencing Project whole-genome sequencing dataset (n = 9,416 cases; 13,603 controls), we conduct ancestry-specific analyses of AD association with GRN genetic variants.
resultsWe report predicted impacts of genetic variation on transcription factor binding for 150 unique transcription factors across the GRN cis-regulatory region. We identify 99 common variants (MAF > 0.005) in one or more superpopulations (African, Admixed American, East Asian, European, and South Asian). The common GRN variant rs5848 is significantly associated with AD only in East Asian ancestry.
conclusionsAncestry-specific effects may contribute to discordant findings in the literature. European-centric results in AD might not be generalizable to other populations.
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