Apr 6, 2020

Tissue-specific multiOMICs analysis of atrial fibrillation

BioRxiv : the Preprint Server for Biology
I. AssumMatthias Heinig


RATIONALE: Genome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. The molecular mechanisms of genotype-phenotype relationships, especially consequences of sequence variants for mRNA and protein expression remain largely elusive. Novel multiOMICs approaches are needed for deciphering the underlying molecular networks. Recently, an omnigenic model postulated the existence of core genes, that accumulate trans regulatory effects and are directly linked to disease phenotypes. However, the existence and identity of AF-relevant core genes remain unknown. OBJECTIVE: The aim was to systematically assess regulatory genetic variants and their downstream consequences on transcriptome, proteome and the disease phenotype AF on a genome-wide scale. METHODS AND RESULTS: We integrated genomics, transcriptomics, and proteomics of human atrial tissue. We identified widespread effects of genetic variants on transcript (cis eQTL) and protein (cis pQTL) abundance of nearby genes with an overrepresentation of GWAS variants for AF. To investigate more complex genetic mechanisms we established a novel approach to identify candidates for AF core genes, as postulated by the omnigenic model...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Pathogenic Organism
Human DNA Sequencing
Statistical Cluster
Sequence Determinations, DNA

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