Tissue-specific multiOMICs analysis of atrial fibrillation

• DOI: 10.1101/2020.04.06.021527
• Publication Date: 2020-04-07T00:36:00Z
• Authors: Ines Assum; Julia Krause; Markus O. Scheinh...; Christian Müller; Elke Hammer; Christin S. Börschel; Uwe Völker; Lenard Conradi; Bastiaan Geelhoed; Tanja Zeller; Renate B. Schnabel; Matthias Heinig
• Keywords: Genome-wide Association Study; Gene regulatory network

Abstract Genome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. Their underlying molecular mechanisms, especially consequences mRNA and protein expression remain largely elusive. Thus, novel multiOMICs approaches are needed deciphering the networks. Here, we integrated genomics, transcriptomics, proteomics of human tissue which allowed identifying widespread effects genetic variants on both transcript (cis eQTL) pQTL) abundance. We further established a targeted trans QTL approach based polygenic risk scores to identify candidates AF core genes. Using this approach, identified two eQTLs four pQTLs GWAS hits, elucidated role transcription factor NKX2-5 as link between SNP rs9481842 AF. Altogether, present an integrative method uncover trans-acting networks in small datasets provide rich resource tissue-specific regulatory levels cardiovascular disease gene prioritization.