Multi-trait association analysis reveals shared genetic loci between Alzheimer's disease and cardiovascular traits.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39537608.
- Also identified by DOI 10.1038/s41467-024-53452-6 and PMC identifier 11561119.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Alzheimer Disease
- Genome-Wide Association Study
- Cardiovascular Diseases
- Polymorphism, Single Nucleotide
- Genetic Predisposition to Disease