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Assum, I. ; Krause, J.* ; Scheinhardt, M.O.* ; Müller, C.* ; Hammer, E.* ; Börschel, C.S.* ; Völker, U.* ; Conradi, L.* ; Geelhoed, B.* ; Zeller, T.* ; Schnabel, R.B.* ; Heinig, M.

Tissue-specific multi-omics analysis of atrial fibrillation.

Nat. Commun. 13:441 (2022)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene-expression; Hypertrophic Cardiomyopathy; Mendelian Randomization; Transcription Factor; Integrative Analysis; Dna Elements; Variants; Identification; Encyclopedia; Metabolism
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 13, Issue: 1, Pages: , Article Number: 441 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Grants "Close the gap" of the UKE
Federal Ministry of Education and Research (BMBF, Germany)
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
European Union's Horizon 2020 research and innovation programme
German Center for Cardiovascular Research (DZHK e.V.)
eMed Network
Federal Ministry of Education and Research