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Single-cell genomics improves the discovery of risk variants and genes of atrial fibrillation.

Single-cell genomics improves the discovery of risk variants and genes of atrial fibrillation.

Authors :
Selewa, Alan
Luo, Kaixuan
Wasney, Michael
Smith, Linsin
Sun, Xiaotong
Tang, Chenwei
Eckart, Heather
Moskowitz, Ivan P.
Basu, Anindita
He, Xin
Pott, Sebastian
Source :
Nature Communications; 8/17/2023, Vol. 14 Issue 1, p1-18, 18p
Publication Year :
2023

Abstract

Genome-wide association studies (GWAS) have linked hundreds of loci to cardiac diseases. However, in most loci the causal variants and their target genes remain unknown. We developed a combined experimental and analytical approach that integrates single cell epigenomics with GWAS to prioritize risk variants and genes. We profiled accessible chromatin in single cells obtained from human hearts and leveraged the data to study genetics of Atrial Fibrillation (AF), the most common cardiac arrhythmia. Enrichment analysis of AF risk variants using cell-type-resolved open chromatin regions (OCRs) implicated cardiomyocytes as the main mediator of AF risk. We then performed statistical fine-mapping, leveraging the information in OCRs, and identified putative causal variants in 122 AF-associated loci. Taking advantage of the fine-mapping results, our novel statistical procedure for gene discovery prioritized 46 high-confidence risk genes, highlighting transcription factors and signal transduction pathways important for heart development. In summary, our analysis provides a comprehensive map of AF risk variants and genes, and a general framework to integrate single-cell genomics with genetic studies of complex traits. Here the authors combine an experimental and analytical approach that integrates single cell epigenomics with GWAS to prioritize risk variants and genes to provide a comprehensive map of Atrial Fibrillation risk variants and genes. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
169997724
Full Text :
https://doi.org/10.1038/s41467-023-40505-5