Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
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 pot...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishiing Group
2018
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| _version_ | 1826262108349661184 |
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| author | Lempiäinen, H Brænne, I Michoel, T Tragante, V Vilne, B Webb, T Kyriakou, T Eichner, J Zeng, L Willenborg, C Franzen, O Ruusalepp, A Goel, A Van Der Laan, S Biegert, C Hamby, S Talukdar, H Foroughi Asl, H Cvgenes@Target Consortium, Pasterkamp, G Watkins, H Samani, N Wittenberger, T Erdmann, J Schunkert, H Asselbergs, F Björkegren, J |
| author_facet | Lempiäinen, H Brænne, I Michoel, T Tragante, V Vilne, B Webb, T Kyriakou, T Eichner, J Zeng, L Willenborg, C Franzen, O Ruusalepp, A Goel, A Van Der Laan, S Biegert, C Hamby, S Talukdar, H Foroughi Asl, H Cvgenes@Target Consortium, Pasterkamp, G Watkins, H Samani, N Wittenberger, T Erdmann, J Schunkert, H Asselbergs, F Björkegren, J |
| author_sort | Lempiäinen, H |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:31:10Z |
| format | Journal article |
| id | oxford-uuid:1d82df5d-1fbf-43ec-b715-9eb408d2a41c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:31:10Z |
| publishDate | 2018 |
| publisher | Nature Publishiing Group |
| record_format | dspace |
| spelling | oxford-uuid:1d82df5d-1fbf-43ec-b715-9eb408d2a41c2022-03-26T11:11:16ZNetwork analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targetsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d82df5d-1fbf-43ec-b715-9eb408d2a41cEnglishSymplectic Elements at OxfordNature Publishiing Group2018Lempiäinen, HBrænne, IMichoel, TTragante, VVilne, BWebb, TKyriakou, TEichner, JZeng, LWillenborg, CFranzen, ORuusalepp, AGoel, AVan Der Laan, SBiegert, CHamby, STalukdar, HForoughi Asl, HCvgenes@Target Consortium,Pasterkamp, GWatkins, HSamani, NWittenberger, TErdmann, JSchunkert, HAsselbergs, FBjörkegren, JGenome-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. |
| spellingShingle | Lempiäinen, H Brænne, I Michoel, T Tragante, V Vilne, B Webb, T Kyriakou, T Eichner, J Zeng, L Willenborg, C Franzen, O Ruusalepp, A Goel, A Van Der Laan, S Biegert, C Hamby, S Talukdar, H Foroughi Asl, H Cvgenes@Target Consortium, Pasterkamp, G Watkins, H Samani, N Wittenberger, T Erdmann, J Schunkert, H Asselbergs, F Björkegren, J Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
| title | Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
| title_full | Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
| title_fullStr | Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
| title_full_unstemmed | Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
| title_short | Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
| title_sort | network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets |
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