@article {7988,
	title = {A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology.},
	journal = {Blood},
	volume = {133},
	year = {2019},
	month = {2019 Feb 28},
	pages = {967-977},
	abstract = {<p>Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a -ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring  messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel ( and ) and 6 known loci associated with FVII activity, explaining 19.0\% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing  in HuH7 cells upregulated FVII, whereas silencing  downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at  and  contribute to FVII activity by regulating  expression levels. FVII activity appears to contribute to the etiology of IS in the general population.</p>},
	issn = {1528-0020},
	doi = {10.1182/blood-2018-05-849240},
	author = {de Vries, Paul S and Sabater-Lleal, Maria and Huffman, Jennifer E and Marten, Jonathan and Song, Ci and Pankratz, Nathan and Bartz, Traci M and de Haan, Hugoline G and Delgado, Graciela E and Eicher, John D and Martinez-Perez, Angel and Ward-Caviness, Cavin K and Brody, Jennifer A and Chen, Ming-Huei and de Maat, Moniek P M and Fr{\r a}nberg, Mattias and Gill, Dipender and Kleber, Marcus E and Rivadeneira, Fernando and Soria, Jos{\'e} Manuel and Tang, Weihong and Tofler, Geoffrey H and Uitterlinden, Andr{\'e} G and van Hylckama Vlieg, Astrid and Seshadri, Sudha and Boerwinkle, Eric and Davies, Neil M and Giese, Anne-Katrin and Ikram, M Kamran and Kittner, Steven J and McKnight, Barbara and Psaty, Bruce M and Reiner, Alex P and Sargurupremraj, Muralidharan and Taylor, Kent D and Fornage, Myriam and Hamsten, Anders and M{\"a}rz, Winfried and Rosendaal, Frits R and Souto, Juan Carlos and Dehghan, Abbas and Johnson, Andrew D and Morrison, Alanna C and O{\textquoteright}Donnell, Christopher J and Smith, Nicholas L}
}
