Instruct: Identify the main category of Medrxiv papers based on the titles and abstracts
Query: Single-cell genomics improves the discovery of risk variants and genes of cardiac traits 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 45 high-confidence risk genes, highlighting transcription factors and signal transduction pathways important for heart development. We further leveraged our single-cell data to study genetics of gene expression. An unexpected finding from earlier studies is that expression QTLs (eQTLs) are often shared across tissues even though most regulatory elements are cell-type specific. We found that this sharing is largely driven by the limited power of eQTL studies using bulk tissues to detect cell-type-specific regulatory variants. This finding points to an important limitation of using eQTLs to interpret GWAS of complex traits. 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.
46
The categories of this paper are: therapeutics
31
The categories of this paper are: imaging
7
The categories of this paper are: emergency
61
The categories of this paper are: dermatology
24
The categories of this paper are: oncology
41
The categories of this paper are: nephrology
51
The categories of this paper are: education
71
The categories of this paper are: ethics
34
The categories of this paper are: therapy
15
The categories of this paper are: allergy
65
The categories of this paper are: oral
0
The categories of this paper are: neurology
33
The categories of this paper are: physical
45
The categories of this paper are: pharmacology
47
The categories of this paper are: care
8
The categories of this paper are: epidemiology