Tissue-specific multi-omics analysis of atrial fibrillation
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Tissue-specific multi-omics analysis of atrial fibrillation. / Assum, Ines; Krause, Julia; Scheinhardt, Markus O; Müller, Christian; Hammer, Elke; Börschel, Christin S; Völker, Uwe; Conradi, Lenard; Geelhoed, Bastiaan; Zeller, Tanja; Schnabel, Renate B; Heinig, Matthias.
in: NAT COMMUN, Jahrgang 13, Nr. 1, 441, 21.01.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Tissue-specific multi-omics analysis of atrial fibrillation
AU - Assum, Ines
AU - Krause, Julia
AU - Scheinhardt, Markus O
AU - Müller, Christian
AU - Hammer, Elke
AU - Börschel, Christin S
AU - Völker, Uwe
AU - Conradi, Lenard
AU - Geelhoed, Bastiaan
AU - Zeller, Tanja
AU - Schnabel, Renate B
AU - Heinig, Matthias
N1 - © 2022. The Author(s).
PY - 2022/1/21
Y1 - 2022/1/21
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-27953-1
DO - 10.1038/s41467-022-27953-1
M3 - SCORING: Journal article
C2 - 35064145
VL - 13
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
M1 - 441
ER -