Publication Date:
2010-11-19
Description:
Abstract 806 Background Factor VIII and von Willebrand factor (vWF) are important components of the coagulation system that circulate together in plasma as a non-covalent complex. Increased circulating levels of FVIII activity (FVIII:C) and vWF antigen (vWF:Ag) in the top 25% of the population distribution are common risk factors for venous thromboembolism, the third leading vascular disease. FVIII and vWF are genetically controlled but their genetic determinants are not fully understood. Moreover, data from populations other than European Americans (EAs) are limited. We performed a genetic association study for plasma levels of FVIII:C and vWF:Ag using a gene-centric approach in the cohorts of NHLBI-funded Candidate gene Association Resource (CARe) consortium. Methods Nearly 50,000 single nucleotide polymorphisms (SNPs) located in about 2,100 candidate genes were genotyped in 18,556 EAs and 4,844 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), Cardiovascular Health Study (CHS), Multi-Ethnic Study of Atherosclerosis (MESA), and Framingham Heart Study (FHS, EAs only). Measurements for FVIII:C and vWF:Ag were inverse normal transformed to normalize trait distribution, and adjusted for age, sex, study site and principal components to account for potential population stratification. Results across studies were combined within each ethnic group by meta-analysis. SNPs with minor allele frequency (MAF)-weighted sample size (MAFxN) 〈 10 were excluded from individual cohorts before the meta-analysis. The threshold for statistical significance was 2.0×10−6 after accounting for the number of independent tests. Results In EAs, four independent regions were identified with p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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