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May 4, 20261 citations

Multi-ancestry transcriptome-wide association study reveals shared and population-specific genetic effects in Alzheimer disease.

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XSXinyu SunMMMakaela MewsNWNicholas R Wheeler

Key Points

  • This study aims to identify genetic effects on Alzheimer disease across different ancestral populations using transcriptome-wide association methods.
  • Conducted a multi-ancestry transcriptome-wide association study (TWAS) to explore associations with Alzheimer disease.
  • Integrated expression quantitative trait loci (eQTL) fine-mapping to enhance understanding of genetic signals.
  • Analyzed data from various populations including non-Hispanic whites (NHW) to assess shared and population-specific effects.
  • Identified a significant association between COG4 expression and Alzheimer disease in non-Hispanic whites.
  • Replicated several genetic signals directionally across multiple ancestries, with strongest support in NHW.
  • Demonstrated that integrated eQTL fine-mapping can refine genetic signals beyond sentinel GWAS variants.

Abstract

≈ 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD.

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Cite This Study

Sun et al. (2026) studied this question.

synapsesocial.com/papers/69f837d73ed186a7399822bchttps://doi.org/10.1016/j.ajhg.2026.04.007
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