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Basic Science and Pathogenesis.

Diya Yang1, Yihe Yang1, Xiaofeng Zhu1

  • 1Case Western Reserve University, Cleveland, OH, USA.

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|December 24, 2025
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Summary
This summary is machine-generated.

Genetic analysis reveals shared genetic architecture between Alzheimer's disease (AD) and kidney function, with specific regions showing strong local correlations. These findings highlight biological pathways influencing both conditions.

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Area of Science:

  • Genetics
  • Neuroscience
  • Nephrology

Background:

  • Alzheimer's disease (AD) and kidney function share risk factors and clearance mechanisms.
  • Kidney function may directly impact AD pathophysiology, independent of cardiovascular factors.
  • Genetic analysis is crucial to understand this relationship, minimizing confounders like age and lifestyle.

Purpose of the Study:

  • To explore the genetic relationship between AD and estimated glomerular filtration rate (eGFR).
  • To identify shared genetic architecture and biological pathways influencing both AD and kidney function.

Main Methods:

  • Genome-wide and local genetic correlations (rg) were analyzed using LDSC, cond/conjFDR, and LAVA.
  • Summary statistics from large-scale genome-wide association studies were utilized.
  • Analyses were conducted in European (EUR) and African (AFR) ancestries.

Main Results:

  • Genome-wide correlations between AD and eGFR were nonsignificant, but strong local correlations were observed in specific regions.
  • In EUR, 52 regions showed significant local correlations, with key signals on chr9 and chr5.
  • Analysis identified pleiotropic loci linked to genes involved in vascular, cognitive, and inflammatory pathways; AFR analysis revealed specific loci with key genes.
  • A significant AFR-specific locus on chr11 contained genes like CD81, STIM1, KCNQ1, and RRM1.

Conclusions:

  • Shared genetic architecture exists between AD and kidney function, driven by specific biological pathways.
  • Findings suggest a complex interplay of concordant and discordant genetic associations.
  • Future research will focus on determining causality and integrating chronic kidney disease associations.