Identification of atrial fibrillation associated genes and functional non-coding variants

Disease-associated genetic variants that lie in non-coding regions found by genome-wide association studies are thought to alter the functionality of transcription regulatory elements and target gene expression. To uncover causal genetic variants, variant regulatory elements and their target genes,...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Nature Communications Ročník 10; číslo 1; s. 4755 - 14
Hlavní autoři:	van Ouwerkerk, Antoinette F., Bosada, Fernanda M., van Duijvenboden, Karel, Hill, Matthew C., Montefiori, Lindsey E., Scholman, Koen T., Liu, Jia, de Vries, Antoine A. F., Boukens, Bastiaan J., Ellinor, Patrick T., Goumans, Marie José T. H., Efimov, Igor R., Nobrega, Marcelo A., Barnett, Phil, Martin, James F., Christoffels, Vincent M.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Springer Science and Business Media LLC 18.10.2019 Nature Publishing Group UK Nature Publishing Group Nature Portfolio
Témata:	38 38/91 631/208/200 631/208/4041 631/337/100 631/337/572/2102 64 64/60 692/4019/592/75 Animals Atrial Fibrillation Atrial Fibrillation - genetics Cardiac arrhythmia Cardiomyocytes Cell Line Chromatin Chromatin - genetics Conformation Connexin 43 Epigenomics Epigenomics - methods Fibrillation Gap junctions Gene expression Gene Expression Profiling Gene Expression Profiling - methods Gene regulation Genes Genetic diversity Genetic Predisposition to Disease Genetic Predisposition to Disease - genetics Genetic variance Genetic Variation Genome-wide association studies Genome-Wide Association Study Genome-Wide Association Study - methods Genomes Heart Atria Heart Atria - cytology Heart Atria - metabolism Homology Humanities and Social Sciences Humans Mice multidisciplinary Myocytes, Cardiac Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Polymorphism, Single Nucleotide Q Regulatory sequences Regulatory Sequences, Nucleic Acid Regulatory Sequences, Nucleic Acid - genetics Science Science (multidisciplinary) Transcription
ISSN:	2041-1723, 2041-1723
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Disease-associated genetic variants that lie in non-coding regions found by genome-wide association studies are thought to alter the functionality of transcription regulatory elements and target gene expression. To uncover causal genetic variants, variant regulatory elements and their target genes, here we cross-reference human transcriptomic, epigenomic and chromatin conformation datasets. Of 104 genetic variant regions associated with atrial fibrillation candidate target genes are prioritized. We optimize EMERGE enhancer prediction and use accessible chromatin profiles of human atrial cardiomyocytes to more accurately predict cardiac regulatory elements and identify hundreds of sub-threshold variants that co-localize with regulatory elements. Removal of mouse homologues of atrial fibrillation-associated regions in vivo uncovers a distal regulatory region involved in Gja1 (Cx43) expression. Our analyses provide a shortlist of genes likely affected by atrial fibrillation-associated variants and provide variant regulatory elements in each region that link genetic variation and target gene regulation, helping to focus future investigations. The majority of disease-associated genetic variants lie in non-coding regions. Here the authors generated and compiled human transcriptomic, epigenomic and chromatin conformation datasets, to identify genes associated with atrial fibrillation and functional non-coding variants.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-12721-5