Characterizing polymorphisms and allelic diversity of von Willebrand factor gene in the 1000 Genomes.

TitleCharacterizing polymorphisms and allelic diversity of von Willebrand factor gene in the 1000 Genomes.
Publication TypeJournal Article
Year of Publication2013
AuthorsWang, QY, Song, J, Gibbs, RA, Boerwinkle, E, Dong, JF, Yu, F
JournalJ Thromb Haemost
Date Published2013 Feb
KeywordsAfrican Americans, African Continental Ancestry Group, Asian Continental Ancestry Group, Databases, Genetic, DNA Mutational Analysis, Ethnic Groups, European Continental Ancestry Group, Gene Frequency, Genetic Predisposition to Disease, Hemostasis, Human Genome Project, Humans, Incidence, Mutation, Phenotype, Polymorphism, Single Nucleotide, von Willebrand Diseases, von Willebrand Factor

BACKGROUND: The von Willebrand factor (VWF) gene is highly polymorphic, with variants correlated with VWF antigen levels, adhesion activity, clearance and factor VIII binding. VWF mutations are detected in patients with von Willebrand disease (VWD), whereas polymorphic variants could be associated with thrombosis. However, information on the ethnic diversity of VWF variants and their association with diseases is limited.

OBJECTIVES: To characterize novel VWF variants from different ethnicities in the general population.

PATIENTS/METHODS: We analyzed samples from 1092 subjects of 14 ethnicities available in the 1000 Genomes database for VWF variants and their potential functional impacts.

RESULTS: We identified 2728 SNPs and 91 insertions and deletions that had a high level of ethnic diversity, with Africans having the highest number of variants. The highest level of diversity was found in the D' and D2 domains. Among 94 non-synonymous variants, 31 were predicted to be deleterious, including 19 that were previously associated with VWD. Most of these 'VWD variants' had allele frequencies consistent with disease incidence in European subjects, but some had a significantly higher frequency in other ethnicities. The mutations R2185Q, H817Q and M740I associated with type 1 and type 2N VWD were present in more than 13% of African subjects.

CONCLUSIONS: These results highlight the complexity of VWF variations in different ethnic groups and emphasize the importance of interrogating variations on multiple ethnic backgrounds for associations with bleeding and thrombosis.

Alternate JournalJ. Thromb. Haemost.
PubMed ID23216583
PubMed Central IDPMC3570679
Grant ListHG003273 / HG / NHGRI NIH HHS / United States
HG005211-01 / HG / NHGRI NIH HHS / United States
HL085769 / HL / NHLBI NIH HHS / United States
HL71895 / HL / NHLBI NIH HHS / United States
MH089175 / MH / NIMH NIH HHS / United States
U01 HG005211 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States