van Loon, J. et al. (2016) Genome-wide association studies identify genetic loci for low von Willebrand factor levels. European Journal of Human Genetics, 24(7), pp. 1035-1040. (doi: 10.1038/ejhg.2015.222) (PMID:26486471)
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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: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Strachan, Mr David and Stott J, Professor David and Rumley, Dr Ann and Lowe, Professor Gordon |
Authors: | van Loon, J., Dehghan, A., Weihong, T., Trompet, S., McArdle, W. L., Asselbergs, F. F.W., Chen, M.-H., Lopez, L. M., Huffman, J. E., Leebeek, F. W.G., Basu, S., Stott, D., Rumley, A., Gansevoort, R. T., Davies, G., Wilson, J. J.F., Witteman, J. C.M., Cao, X., de Craen, A. J.M., Bakker, S. J.L., Psaty, B. M., Starr, J. M., Hofman, A., Wouter Jukema, J., Deary, I. J., Hayward, C., van der Harst, P., Lowe, G. D.O., Folsom, A. R., Strachan, D. P., Smith, N., de Maat, M. P.M., and O'Donnell, C. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | European Journal of Human Genetics |
Publisher: | Nature Publishing Group |
ISSN: | 1018-4813 |
ISSN (Online): | 1476-5438 |
Published Online: | 21 October 2015 |
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