Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits
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 cardiovasc...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53452-6 |
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| author | Fotios Koskeridis Nurun Fancy Pei Fang Tan Devendra Meena Evangelos Evangelou Paul Elliott Dennis Wang Paul M. Matthews Abbas Dehghan Ioanna Tzoulaki |
| author_facet | Fotios Koskeridis Nurun Fancy Pei Fang Tan Devendra Meena Evangelos Evangelou Paul Elliott Dennis Wang Paul M. Matthews Abbas Dehghan Ioanna Tzoulaki |
| author_sort | Fotios Koskeridis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b7f6e2bef1bb4252a2be241b198e6687 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b7f6e2bef1bb4252a2be241b198e66872024-11-17T12:35:47ZengNature PortfolioNature Communications2041-17232024-11-0115111210.1038/s41467-024-53452-6Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traitsFotios Koskeridis0Nurun Fancy1Pei Fang Tan2Devendra Meena3Evangelos Evangelou4Paul Elliott5Dennis Wang6Paul M. Matthews7Abbas Dehghan8Ioanna Tzoulaki9Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonUK Dementia Research Institute, Imperial College LondonInstitute for Human Development and Potential, Agency for Science, Technology and Research (A*STAR)Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonInstitute for Human Development and Potential, Agency for Science, Technology and Research (A*STAR)UK Dementia Research Institute, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonAbstract 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.https://doi.org/10.1038/s41467-024-53452-6 |
| spellingShingle | Fotios Koskeridis Nurun Fancy Pei Fang Tan Devendra Meena Evangelos Evangelou Paul Elliott Dennis Wang Paul M. Matthews Abbas Dehghan Ioanna Tzoulaki Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits Nature Communications |
| title | Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits |
| title_full | Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits |
| title_fullStr | Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits |
| title_full_unstemmed | Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits |
| title_short | Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits |
| title_sort | multi trait association analysis reveals shared genetic loci between alzheimer s disease and cardiovascular traits |
| url | https://doi.org/10.1038/s41467-024-53452-6 |
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