Abstract

During the past decade, genome-wide association studies (GWAS) have identified many genetic variants with susceptibility to several thousands of complex diseases or traits. The genetic regulation of gene expression is highly tissue-specific and cell type-specific. Recently, single-cell technology has paved the way to dissect cellular heterogeneity in human tissues. Here, we present a reference database for GWAS trait-associated cell type-specificity, named Cell type-Specific Enrichment Analysis DataBase (CSEA-DB, available at https://bioinfo.uth.edu/CSEADB/). Specifically, we curated total of 5120 GWAS summary statistics data for a wide range of human traits and diseases followed by rigorous quality control. We further collected >900 000 cells from the leading consortia such as Human Cell Landscape, Human Cell Atlas, and extensive literature mining, including 752 tissue cell types from 71 adult and fetal tissues across 11 human organ systems. The tissues and cell types were annotated with Uberon and Cell Ontology. By applying our deTS algorithm, we conducted 10 250 480 times of trait-cell type associations, reporting a total of 598 (11.68%) GWAS traits with at least one significantly associated cell type. In summary, CSEA-DB could serve as a repository of association map for human complex traits and their underlying cell types, manually curated GWAS, and single-cell transcriptome resources.

中文翻译：

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CSEA-DB：人类复杂特征和细胞类型关联的综合体

摘要

在过去的十年中，全基因组关联研究（GWAS）确定了许多易受数千种复杂疾病或性状影响的遗传变异。基因表达的遗传调控是高度组织特异性和细胞类型特异性的。最近，单细胞技术为解剖人体组织中的细胞异质性铺平了道路。在这里，我们介绍了一个与GWAS性状相关的细胞类型特异性的参考数据库，称为细胞类型特异性富集分析数据库（CSEA-DB，可从https://bioinfo.uth.edu/CSEADB/获得）。具体而言，我们精心挑选了总计5120个GWAS汇总统计数据，用于各种人类特征和疾病，然后进行严格的质量控制。我们进一步从领先的财团（如人类细胞景观，人类细胞图集，以及广泛的文献挖掘，包括11种人体器官系统中来自71个成年和胎儿组织的752种组织细胞类型。用Uberon和Cell Ontology注释组织和细胞类型。通过应用我们的deTS算法，我们进行了10 250 480次性状-细胞类型关联，报告了总共598（11.68％）GWAS性状与至少一种显着相关的细胞类型。总之，CSEA-DB可以用作人类复杂性状及其基础细胞类型，人工策划的GWAS和单细胞转录组资源的关联图存储库。共有598（11.68％）个GWAS性状与至少一种明显相关的细胞类型相关。总之，CSEA-DB可以用作人类复杂性状及其基础细胞类型，人工策划的GWAS和单细胞转录组资源的关联图存储库。共有598（11.68％）个GWAS性状与至少一种明显相关的细胞类型相关。总之，CSEA-DB可以用作人类复杂性状及其基础细胞类型，人工策划的GWAS和单细胞转录组资源的关联图存储库。