van Loon, Janine and Dehghan, Abbas and Weihong, Tang and Trompet, Stella and McArdle, Wendy L and Asselbergs, Folkert F W and Chen, Ming-Huei and Lopez, Lorna M and Huffman, Jennifer E and Leebeek, Frank W G and Basu, Saonli and Stott, David J and Rumley, Ann and Gansevoort, Ron T and Davies, Gail and Wilson, James J F and Witteman, Jacqueline C M and Cao, Xiting and de Craen, Anton J M and Bakker, Stephan J L and Psaty, Bruce M and Starr, John M and Hofman, Albert and Wouter Jukema, J and Deary, Ian J and Hayward, Caroline and van der Harst, Pim and Lowe, Gordon D O and Folsom, Aaron R and Strachan, David P and Smith, Nicolas and 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:	https://doi.org/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
URI:	Publisher
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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