You are here

{A genetic association study of circulating coagulation Factor VIII and von Willebrand Factor levels

Title{A genetic association study of circulating coagulation Factor VIII and von Willebrand Factor levels
Publication TypeJournal Article
Year of Publication2024
Authorsde Vries, PS, Reventun, P, Brown, MR, Heath, AS, Huffman, JE, Le, NQ, Bebo, A, Brody, JA, Temprano-Sagrera, G, Raffield, LM, Ozel, AB, Thibord, F, Jain, D, Lewis, JP, Rodriguez, BAT, Pankratz, N, Taylor, KD, Polasek, O, Chen, MH, Yanek, LR, Carrasquilla, GD, Marioni, R, Kleber, ME, t, DA, Yao, J, Li-Gao, R, Joshi, PK, Trompet, S, Martinez-Perez, A, Ghanbari, M, Howard, TE, Reiner, AP, Arvanitis, M, Ryan, KA, Bartz, TM, Rudan, I, Faraday, N, Linneberg, A, Ekunwe, L, Davies, G, Delgado, GE, Suchon, P, Guo, X, Rosendaal, FR, Klaric, L, Noordam, R, van Rooij, F, Curran, JE, Wheeler, MM, Osburn, WO, O'Connell, JR, Boerwinkle, E, Beswick, A, Psaty, BM, Kolcic, I, Souto, JC, Becker, LC, Hansen, T, Doyle, MF, Harris, SE, Moissl, AP, Deleuze, JF, Rich, SS, A. Vlieg, vanHylckama, Campbell, H, Stott, DJ, Soria, JM, de Maat, MPM, Almasy, L, Brody, LC, Auer, PL, Mitchell, BD, Ben-Shlomo, Y, Fornage, M, Hayward, C, Mathias, RA, inen, TO, Lange, LA, Cox, SR, rz, W, Morange, PE, Rotter, JI, Mook-Kanamori, DO, Wilson, JF, van der Harst, P, Jukema, JW, Ikram, MA, Blangero, J, Kooperberg, C, Desch, KC, Johnson, AD, Sabater-Lleal, M, Lowenstein, CJ, Smith, NL, Morrison, AC
JournalBlood
Date PublishedFeb
Abstract10-9) at seven new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and one for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multi-phenotype analysis of FVIII and VWF identified another three new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, while silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and one for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.
ePub date: 
24/02