| Autor: |
Francis J.A. Leblanc, Xuexin Jin, Kai Kang, Chang Jie Mick Lee, Juan Xu, Lina Xuan, Wenbo Ma, Hicham Belhaj, Marouane Benzaki, Neelam Mehta, Roger Sik Yin Foo, Svetlana Reilly, Chukwuemeka George Anene-Nzelu, Zhenwei Pan, Stanley Nattel, Baofeng Yang, Guillaume Lettre |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
iScience, Vol 27, Iss 9, Pp 110660- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.110660 |
| Popis: |
Summary: Atrial fibrillation (AF) is the most common arrhythmia in the world. Human genetics can provide strong AF therapeutic candidates, but the identification of the causal genes and their functions remains challenging. Here, we applied an AF fine-mapping strategy that leverages results from a previously published cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAAs) obtained from two cohorts with distinct ancestry, and a paired RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) LAA single-nucleus assay (sn-multiome). At nine AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Data integration identified several candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at MAPT. Finally, we showed that the repression of the strongest AF-associated eQTL gene, LINC01629, in human embryonic stem cell-derived cardiomyocytes using CRISPR inhibition results in the dysregulation of pathways linked to genes involved in the development of atrial tissue and the cardiac conduction system. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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