Journal article
Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
- Abstract:
- Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular tissue gene-protein sub-networks ("modules"). The modules and genes within were scored for CAD druggability potential. The scoring enriched for targets of cardiometabolic drugs currently in clinical use and in-depth analysis of the top-scoring modules validated established and revealed novel target tissues, biological processes, and druggable targets. This study provides an unprecedented resource of tissue-defined gene-protein interactions directly affected by genetic variance in CAD risk loci.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.3MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-018-20721-6
Authors
+ European Union Seventh Framework Programme
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- Grant:
- FP7/2007–2013 under grant agreement n° HEALTH-F2-2013-601456
- Publisher:
- Nature Publishiing Group
- Journal:
- Scientific Reports More from this journal
- Volume:
- 8
- Pages:
- 3434
- Publication date:
- 2018-02-21
- Acceptance date:
- 2017-12-06
- DOI:
- EISSN:
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2045-2322
- ISSN:
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2045-2322
- Pmid:
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29467471
- Language:
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English
- Keywords:
- Pubs id:
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pubs:826073
- UUID:
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uuid:1d82df5d-1fbf-43ec-b715-9eb408d2a41c
- Local pid:
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pubs:826073
- Source identifiers:
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826073
- Deposit date:
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2018-08-23
Terms of use
- Copyright holder:
- Lempiäinen et al
- Copyright date:
- 2018
- Notes:
- © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium orformat, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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