Title | A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | de 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 |
Journal | Blood |
Volume | 143 |
Issue | 18 |
Pagination | 1845-1855 |
Date Published | 2024 May 02 |
ISSN | 1528-0020 |
Keywords | Cell 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 |
DOI | 10.1182/blood.2023021452 |
Alternate Journal | Blood |
PubMed ID | 38320121 |
PubMed Central ID | PMC11443575 |
Grant List | MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom R01 HL139553 / HL / NHLBI NIH HHS / United States |
A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.
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