Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases.
Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases.
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全血的全基因组 DNA 和 RNA 测序阐明了多种疾病背后的基因表达的遗传结构。
DOI：
10.1101/2022.04.13.22273841
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Pelos
中科院分区：
文献类型：
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作者：
Liu,Chunyu;Joehanes,Roby;Ma,Jiantao;Wang,Yuxuan;Sun,Xianbang;Keshawarz,Amena;Sooda,Meera;Huan,Tianxiao;Hwang,Shih-Jen;Bui,Helena;Tejada,Brandon;Munson,PeterJ;Cumhur,Demirkale;Heard-Costa,NancyL;Pitsillides,AchilleasN;Pelos
为了创建表达定量追踪基因座（eQTL）的科学资源，我们使用从Frachial Heart研究的2622名参与者的DNA的全基因组测序（WGS）获得的基因型和从全血的RNA测序（RNA-seq）获得的基因表达水平进行了全基因组关联研究（GWAS）。我们鉴定了6，778，286个顺式eQTL变异体-基因转录本（eGene）对（p < 5 × 10-8）（2，855，111个顺式eQTL变异体和15，982个独特eGene）和1，469，754个反式eQTL变异体-eGene对（p <1 e-12）（526，056个独特反式eQTL变异体和7233个独特eGene）。此外，442，379个cis-eQTL变异与1518个长非蛋白质编码RNA（lncRNA）的表达相关。基因本体论（GO）分析揭示，前GO术语forcis-eGenes富集免疫功能（FDR < 0.05）。Thecis-eQTL变异体富含据报道与先前GWAS中的815个性状相关的SNP，包括心血管疾病风险因素。作为概念证明，我们在因果推断测试中使用该eQTL资源与来自公共GWAS数据库的遗传变体（例如，COVID-19严重程度）。在Bonferroni校正后，孟德尔随机化分析确定了60个eGenes与收缩压的假定因果关系，13个基因与冠状动脉疾病，7个基因与COVID-19严重程度。这项研究通过BioData Catalyst创建了一个全面的eQTL资源，将提供给科学界。这将促进对广泛疾病的基因表达的遗传结构的理解。
To create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene expression levels from RNA sequencing (RNA-seq) of whole blood in 2622 participants in Framingham Heart Study. We identified 6,778,286cis-eQTL variant-gene transcript (eGene) pairs atp< 5 × 10–8(2,855,111 uniquecis-eQTL variants and 15,982 unique eGenes) and 1,469,754trans-eQTL variant-eGene pairs atp< 1e−12 (526,056 uniquetrans-eQTL variants and 7233 unique eGenes). In addition, 442,379cis-eQTL variants were associated with expression of 1518 long non-protein coding RNAs (lncRNAs). Gene Ontology (GO) analyses revealed that the top GO terms forcis-eGenes are enriched for immune functions (FDR < 0.05). Thecis-eQTL variants are enriched for SNPs reported to be associated with 815 traits in prior GWAS, including cardiovascular disease risk factors. As proof of concept, we used this eQTL resource in conjunction with genetic variants from public GWAS databases in causal inference testing (e.g., COVID-19 severity). After Bonferroni correction, Mendelian randomization analyses identified putative causal associations of 60 eGenes with systolic blood pressure, 13 genes with coronary artery disease, and seven genes with COVID-19 severity. This study created a comprehensive eQTL resource via BioData Catalyst that will be made available to the scientific community. This will advance understanding of the genetic architecture of gene expression underlying a wide range of diseases.