期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 24, 期 7, 页码 1035-1040出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2015.222
关键词
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资金
- National Heart, Lung and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, UL1RR025005, 2R01LM010098]
- NIH Roadmap for Medical Research
- Medical Research Council [G0000934]
- Wellcome Trust [068545/Z/02]
- UK's Biotechnology and Biological Sciences Research Council (BBSRC)
- Chief Scientist Office of the Scottish Government [ETM/55]
- Research Into Ageing, Age UK's The Disconnected Mind project
- UK's BBSRC
- EPSRC
- ESRC
- MRC
- Scottish Executive Chief Scientist Office
- Health Services Research Committee [CZG/4/306]
- Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [NGI/NOW 911-03-016]
- Erasmus Medical Center
- Erasmus University Rotterdam
- Netherlands Organization for Scientific Research
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly
- Netherlands Heart Foundation [DHF-2007B159]
- Ministry of Education, Culture and Science
- Ministry of Health Welfare and Sports
- European Commission
- Municipality of Rotterdam
- Netherlands Organization for Scientific Research (NWO) [175.010.2005.011, 911.03.012]
- Research Institute for Diseases in the Elderly (RIDE)
- Netherlands Genomics Initiative (NGI)/NWO [050-060-810]
- NWO/ZonMw [918-76-619]
- NWO Grant (veni) [916.12.154]
- EUR Fellowship
- Dutch Kidney Foundation [E033]
- EU project grant GENECURE [FP-6 LSHM CT 2006 037697]
- Netherlands Organization for Health Research and Development (NWO-Groot Grant) [175.010.2007.006]
- NWO VENI Grant [916.761.70]
- ZonMw Grant [90.700.441]
- Dutch Inter-University Cardiology Institute Netherlands (ICIN)
- Medical Research Council UK
- Ministry of Science, Education and Sport of the Republic of Croatia [108-1080315-0302]
- European Union framework program 6 EUROSPAN project [LSHG-CT-2006-018947]
- Chief Scientist Office of the Scottish Government
- Royal Society
- BBSRC [BB/F019394/1] Funding Source: UKRI
- MRC [MR/N01104X/1, MC_PC_U127561128, G0700704, G1001799, G0000934] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish
- Chief Scientist Office [ETM/55] Funding Source: researchfish
- Medical Research Council [G1001799, MR/N01104X/1, G0000934, G0700704, MR/K026992/1, MC_PC_U127561128] Funding Source: researchfish
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 x 10(-8) and comprised five loci on four different chromosomes: 6q24 (smallest P-value 5.8 x 10(-10)), 9q34 (2.4 x 10(-64)), 12p13 (5.3x 10(-22)), 12q23 (1.2 x 10(-8)) and 13q13 (2.6 x 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.
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