| Title: | Genome-wide association and multi-omic analyses reveal ACTN2 as a gene linked to heart failure |
| Journal: | Nature Communications |
| Published: | 28 Feb 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32111823/ |
| DOI: | https://doi.org/10.1038/s41467-020-14843-7 |
| URL: | https://www.nature.com/articles/s41467-020-14843-7.pdf |
Publication 7638
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Abstract
Heart failure is a major public health problem affecting over 23 million people worldwide. In this study, we present the results of a large scale meta-analysis of heart failure GWAS and replication in a comparable sized cohort to identify one known and two novel loci associated with heart failure. Heart failure sub-phenotyping shows that a new locus in chromosome 1 is associated with left ventricular adverse remodeling and clinical heart failure, in response to different initial cardiac muscle insults. Functional characterization and fine-mapping of that locus reveal a putative causal variant in a cardiac muscle specific regulatory region activated during cardiomyocyte differentiation that binds to the ACTN2 gene, a crucial structural protein inside the cardiac sarcolemma (Hi-C interaction p-value = 0.00002). Genome-editing in human embryonic stem cell-derived cardiomyocytes confirms the influence of the identified regulatory region in the expression of ACTN2. Our findings extend our understanding of biological mechanisms underlying heart failure.13 Authors
- Marios Arvanitis
- Emmanouil Tampakakis
- Yanxiao Zhang
- Wei Wang
- Adam Auton
- Diptavo Dutta
- Stephanie Glavaris
- Ali Keramati
- Nilanjan Chatterjee
- Neil C. Chi
- Bing Ren
- Wendy S. Post
- Alexis Battle
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