Multi-trait Association Analysis Reveals Shared Genetic Loci Between Alzheimer's Disease and Cardiovascular Traits

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 13

PMID 39537608

Authors

Fotios Koskeridis

Nurun Fancy

Pei Fang Tan

Devendra Meena

Evangelos Evangelou

Paul Elliott

Dennis Wang

Paul M Matthews

Abbas Dehghan

Ioanna Tzoulaki

Affiliations

Soon will be listed here.

Abstract

Several cardiovascular traits and diseases co-occur with Alzheimer's disease. We mapped their shared genetic architecture using multi-trait genome-wide association studies. Subsequent fine-mapping and colocalisation highlighted 16 genetic loci associated with both Alzheimer's and cardiovascular diseases. We prioritised rs11786896, which colocalised with Alzheimer's disease, atrial fibrillation and expression of PLEC in the heart left ventricle, and rs7529220, which colocalised with Alzheimer's disease, atrial fibrillation and expression of C1Q family genes. Single-cell RNA-sequencing data, co-expression network and protein-protein interaction analyses provided evidence for different mechanisms of PLEC, which is upregulated in left ventricular endothelium and cardiomyocytes with heart failure and in brain astrocytes with Alzheimer's disease. Similar common mechanisms are implicated for C1Q in heart macrophages with heart failure and in brain microglia with Alzheimer's disease. These findings highlight inflammatory and pleomorphic risk determinants for the co-occurrence of Alzheimer's and cardiovascular diseases and suggest PLEC, C1Q and their interacting proteins as potential therapeutic targets.

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