Common and Rare Variants in Genes Associated with von Willebrand Factor Level Variation: No Accumulation of Rare Variants in Swedish von Willebrand Disease Patients.

ABSTRACT: Genome-wide association studies (GWASs) have identified genes that affect plasma von Willebrand factor (VWF) levels. ABO showed a strong effect, whereas smaller effects were seen for VWF , STXBP5 , STAB2 , SCARA5 , STX2 , TC2N , and CLEC4M . This study screened comprehensively for both common and rare variants in these eight genes by resequencing their coding sequences in 104 Swedish von Willebrand disease (VWD) patients. The common variants previously associated with the VWF level were all accumulated in the VWD patients compared to three control populations. The strongest effect was detected for blood group O coded for by the ABO gene (71 vs. 38% of genotypes). The other seven VWF level associated alleles were enriched in the VWD population compared to control populations, but the differences were small and not significant. The sequencing detected a total of 146 variants in the eight genes. Excluding 70 variants in VWF , 76 variants remained. Of the 76 variants, 54 had allele frequencies?>?0.5% and have therefore been investigated for their association with the VWF level in previous GWAS. The remaining 22 variants with frequencies?

SUBMITTER: Manderstedt E 

PROVIDER: S-EPMC7603419 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature