TY - JOUR
T1 - Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
AU - CVgenes@target consortium
AU - Lempiäinen, Harri
AU - Brænne, Ingrid
AU - Michoel, Tom
AU - Tragante, Vinicius
AU - Vilne, Baiba
AU - Webb, Tom R
AU - Kyriakou, Theodosios
AU - Eichner, Johannes
AU - Zeng, Lingyao
AU - Willenborg, Christina
AU - Franzen, Oscar
AU - Ruusalepp, Arno
AU - Goel, Anuj
AU - Van Der Laan, Sander W.
AU - Biegert, Claudia
AU - Hamby, Stephen E.
AU - Talukdar, Husain A.
AU - Foroughi Asl, Hassan
AU - Pasterkamp, Gerard
AU - Watkins, Hugh
AU - Samani, Nilesh J
AU - Wittenberger, Timo
AU - Erdmann, Jeanette
AU - Schunkert, Heribert
AU - Asselbergs, Folkert W.
AU - Björkegren, Johan L M
PY - 2018/2/21
Y1 - 2018/2/21
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/s41598-018-20721-6
DO - 10.1038/s41598-018-20721-6
M3 - Article
C2 - 29467471
SN - 2045-2322
VL - 8
SP - 3434
JO - Scientific Reports
JF - Scientific Reports
IS - 1
ER -