Imperial College London
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ProfessorAbbasDehghan

Faculty of Medicine, School of Public Health

Professor in Molecular Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stacey:2022:10.1038/s41467-022-28729-3,
author = {Stacey, D and Chen, L and Stanczyk, P and Howson, J and Mason, A and Burgess, S and MacDonald, S and Langdown, J and McKinney, H and Downes, K and Farahi, N and Peters, J and Basu, S and Pankow, JS and Tang, W and Pankratz, N and Sabater-Lleal, M and De, Vries PS and Smith, NL and CHARGE, Hemostasis Working Group and Gelinas, AD and Schneider, DJ and Janjie, N and Samani, NJ and Ye, S and Summers, C and Chilvers, E and Danesh, J and Paul, D},
doi = {10.1038/s41467-022-28729-3},
journal = {Nature Communications},
title = {Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus},
url = {http://dx.doi.org/10.1038/s41467-022-28729-3},
volume = {13},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Many individual genetic risk loci have been associated with multiple common human diseases. However, themolecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal themolecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) riskbut higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variantat the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitroexperimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C throughendothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte–endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CADthrough anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides aframework to reveal the mechanisms underlying similar cross-phenotype associations.
AU  - Stacey,D
AU  - Chen,L
AU  - Stanczyk,P
AU  - Howson,J
AU  - Mason,A
AU  - Burgess,S
AU  - MacDonald,S
AU  - Langdown,J
AU  - McKinney,H
AU  - Downes,K
AU  - Farahi,N
AU  - Peters,J
AU  - Basu,S
AU  - Pankow,JS
AU  - Tang,W
AU  - Pankratz,N
AU  - Sabater-Lleal,M
AU  - De,Vries PS
AU  - Smith,NL
AU  - CHARGE,Hemostasis Working Group
AU  - Gelinas,AD
AU  - Schneider,DJ
AU  - Janjie,N
AU  - Samani,NJ
AU  - Ye,S
AU  - Summers,C
AU  - Chilvers,E
AU  - Danesh,J
AU  - Paul,D
DO  - 10.1038/s41467-022-28729-3
PY  - 2022///
SN  - 2041-1723
TI  - Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-022-28729-3
UR  - https://www.nature.com/articles/s41467-022-28729-3
UR  - http://hdl.handle.net/10044/1/95270
VL  - 13
ER  -
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