A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.

TitleA 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, N-Q, Bebo, A, Brody, JA, Temprano-Sagrera, G, Raffield, LM, Ozel, ABilge, Thibord, F, Jain, D, Lewis, JP, Rodriguez, BAT, Pankratz, N, Taylor, KD, Polasek, O, Chen, M-H, Yanek, LR, Carrasquilla, GD, Marioni, RE, Kleber, ME, Trégouët, D-A, 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, JCarlos, Becker, LC, Hansen, T, Doyle, MF, Harris, SE, Moissl, AP, Deleuze, J-F, Rich, SS, Vlieg, Avan Hylcka, Campbell, H, Stott, DJ, Soria, JManuel, de Maat, MPM, Almasy, L, Brody, LC, Auer, PL, Mitchell, BD, Ben-Shlomo, Y, Fornage, M, Hayward, C, Mathias, RA, Kilpeläinen, TO, Lange, LA, Cox, SR, Marz, W, Morange, P-E, Rotter, JI, Mook-Kanamori, DO, Wilson, JF, van der Harst, P, J Jukema, W, M Ikram, A, Blangero, J, Kooperberg, C, Desch, KC, Johnson, AD, Sabater-Lleal, M, Lowenstein, CJ, Smith, NL, Morrison, AC
JournalBlood
Volume143
Issue18
Pagination1845-1855
Date Published2024 May 02
ISSN1528-0020
KeywordsCell Adhesion Molecules, Endothelial Cells, Factor VIII, Female, Genetic Association Studies, Genome-Wide Association Study, Human Umbilical Vein Endothelial Cells, Humans, Kininogens, Lectins, C-Type, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Receptors, Cell Surface, Thrombosis, von Willebrand Factor
Abstract

Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P

DOI10.1182/blood.2023021452
Alternate JournalBlood
PubMed ID38320121
Grant ListMC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
R01 HL139553 / HL / NHLBI NIH HHS / United States

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