{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Assum I"],"funding":["Bundesministerium für Bildung und Forschung"],"pagination":["441"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8782899"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Genome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. Their underlying molecular mechanisms, especially consequences for mRNA and protein expression remain largely elusive. Thus, refined multi-omics approaches are needed for deciphering the underlying molecular networks. Here, we integrate genomics, transcriptomics, and proteomics of human atrial tissue in a cross-sectional study to identify widespread effects of genetic variants on both transcript (cis-eQTL) and protein (cis-pQTL) abundance. We further establish a novel targeted trans-QTL approach based on polygenic risk scores to determine candidates for AF core genes. Using this approach, we identify two trans-eQTLs and five trans-pQTLs for AF GWAS hits, and elucidate the role of the transcription factor NKX2-5 as a link between the GWAS SNP rs9481842 and AF. Altogether, we present an integrative multi-omics method to uncover trans-acting networks in small datasets and provide a rich resource of atrial tissue-specific regulatory variants for transcript and protein levels for cardiovascular disease gene prioritization."],"journal":["Nature communications"],"pubmed_title":["Tissue-specific multi-omics analysis of atrial fibrillation."],"pmcid":["PMC8782899"],"funding_grant_id":["01ZX1408D","01ZX1708G"],"pubmed_authors":["Zeller T","Schnabel RB","Geelhoed B","Conradi L","Borschel CS","Muller C","Hammer E","Heinig M","Krause J","Scheinhardt MO","Volker U","Assum I"],"additional_accession":[]},"is_claimable":false,"name":"Tissue-specific multi-omics analysis of atrial fibrillation.","description":"Genome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. Their underlying molecular mechanisms, especially consequences for mRNA and protein expression remain largely elusive. Thus, refined multi-omics approaches are needed for deciphering the underlying molecular networks. Here, we integrate genomics, transcriptomics, and proteomics of human atrial tissue in a cross-sectional study to identify widespread effects of genetic variants on both transcript (cis-eQTL) and protein (cis-pQTL) abundance. We further establish a novel targeted trans-QTL approach based on polygenic risk scores to determine candidates for AF core genes. Using this approach, we identify two trans-eQTLs and five trans-pQTLs for AF GWAS hits, and elucidate the role of the transcription factor NKX2-5 as a link between the GWAS SNP rs9481842 and AF. Altogether, we present an integrative multi-omics method to uncover trans-acting networks in small datasets and provide a rich resource of atrial tissue-specific regulatory variants for transcript and protein levels for cardiovascular disease gene prioritization.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-06-19T03:17:52.948Z","creation":"2025-02-19T03:53:30.47Z"},"accession":"S-EPMC8782899","cross_references":{"pubmed":["35064145"],"doi":["10.1038/s41467-022-27953-1"]}}