Sabater-Lleal M, et al. - Given that factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are linked with risk of arterial and venous thrombosis and with hemorrhagic disorders, researchers examined and functionally tested novel genetic associations regulating plasma FVIII and VWF by meta-analyzing genome-wide association results from 46,354 individuals of European, African, East Asian, and Hispanic ancestry. Using an additive genetic model, all studies performed linear regression analysis. Additional evidence on association and function was obtained by performing in vitro gene silencing in cultured endothelial cells for candidate genes. Findings revealed 13 novel genome-wide significant associations, 7 with FVIII levels (FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels (PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA); this is in addition to 10 previously reported associations with these phenotypes. Except ARSA and DAB2IP, further evidence of association for all loci on VWF was obtained through functional validation. Some evidence was found for a causal role of these proteins in thrombotic events.