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    Genome-wide association studies identify genetic loci for low von Willebrand factor levels


    van Loon, Janine, Dehghan, Abbas, Weihong, Tang, Trompet, Stella, McArdle, Wendy L, Asselbergs, Folkert F W, Chen, Ming-Huei, Lopez, Lorna M, Huffman, Jennifer E, Leebeek, Frank W G, Basu, Saonli, Stott, David J, Rumley, Ann, Gansevoort, Ron T, Davies, Gail, Wilson, James J F, Witteman, Jacqueline C M, Cao, Xiting, de Craen, Anton J M, Bakker, Stephan J L, Psaty, Bruce M, Starr, John M, Hofman, Albert, Wouter Jukema, J, Deary, Ian J, Hayward, Caroline, van der Harst, Pim, Lowe, Gordon D O, Folsom, Aaron R, Strachan, David P, Smith, Nicolas, de Maat, Moniek P M and O'Donnell, Christopher (2016) Genome-wide association studies identify genetic loci for low von Willebrand factor levels. European Journal of Human Genetics, 24 (7). pp. 1035-1040. ISSN 1018-4813

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    Abstract

    Low von Willebrand factor (VWF) levels are associated with bleeding symptoms and are a diagnostic criterion for von Willebrand disease, the most common inherited bleeding disorder. To date, it is unclear which genetic loci are associated with reduced VWF levels. Therefore, we conducted a meta-analysis of genome-wide association studies to identify genetic loci associated with low VWF levels. For this meta-analysis, we included 31 149 participants of European ancestry from 11 community-based studies. From all participants, VWF antigen (VWF:Ag) measurements and genome-wide single-nucleotide polymorphism (SNP) scans were available. Each study conducted analyses using logistic regression of SNPs on dichotomized VWF:Ag measures (lowest 5% for blood group O and non-O) with an additive genetic model adjusted for age and sex. An inverse-variance weighted meta-analysis was performed for VWF:Ag levels. A total of 97 SNPs exceeded the genome-wide significance threshold of 5 × 10−8 and comprised five loci on four different chromosomes: 6q24 (smallest P-value 5.8 × 10−10), 9q34 (2.4 × 10−64), 12p13 (5.3 × 10−22), 12q23 (1.2 × 10−8) and 13q13 (2.6 × 10−8). All loci were within or close to genes, including STXBP5 (Syntaxin Binding Protein 5) (6q24), STAB5 (stabilin-5) (12q23), ABO (9q34), VWF (12p13) and UFM1 (ubiquitin-fold modifier 1) (13q13). Of these, UFM1 has not been previously associated with VWF:Ag levels. Four genes that were previously associated with VWF levels (VWF, ABO, STXBP5 and STAB2) were also associated with low VWF levels, and, in addition, we identified a new gene, UFM1, that is associated with low VWF levels. These findings point to novel mechanisms for the occurrence of low VWF levels.
    Item Type: Article
    Keywords: Genome-wide; association studies; identify; genetic loci; low von Willebrand factor levels;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17196
    Identification Number: 10.1038/ejhg.2015.222
    Depositing User: Lorna Lopez
    Date Deposited: 17 May 2023 10:11
    Journal or Publication Title: European Journal of Human Genetics
    Publisher: Springer Nature
    Refereed: Yes
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17196
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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