Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits

Fotios Koskeridis (), Nurun Fancy, Pei Fang Tan, Devendra Meena, Evangelos Evangelou, Paul Elliott, Dennis Wang, Paul M. Matthews, Abbas Dehghan and Ioanna Tzoulaki
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Fotios Koskeridis: Imperial College London
Nurun Fancy: Imperial College London
Pei Fang Tan: Technology and Research (A*STAR)
Devendra Meena: Imperial College London
Evangelos Evangelou: Imperial College London
Paul Elliott: Imperial College London
Dennis Wang: Technology and Research (A*STAR)
Paul M. Matthews: Imperial College London
Abbas Dehghan: Imperial College London
Ioanna Tzoulaki: Imperial College London

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53452-6

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