Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project
Year: 2013
Type: article
Study design: Observational Study
Abstract: Several rare European von Willebrand disease missense variants of VWF (including p.Arg2185Gln and p.His817Gln) were recently reported to be common in apparently healthy African Americans (AAs). Using data from the NHLBI Exome Sequencing Project, we assessed the association of these and other VWF coding variants with von Willebrand factor (VWF) and factor VIII (FVIII) levels in 4468 AAs. Of 30 nonsynonymous VWF variants, 6 were significantly and independently associated (P < .001) with levels of VWF and/or FVIII. Each additional copy of the common VWF variants encoding p.Thr789Ala or p.Asp1472His was associated with 6 to 8 IU/dL higher VWF levels. The VWF variant encoding p.Arg2185Gln was associated with 7 to 13 IU/dL lower VWF and FVIII levels. The type 2N-related VWF variant encoding p.His817Gln was associated with 17 IU/dL lower FVIII level but normal VWF level. A novel, rare missense VWF variant that predicts disruption of an O-glycosylation site (p.Ser1486Leu) and a rare variant encoding p.Arg2287Trp were each associated with 30 to 40 IU/dL lower VWF level (P < .001). In summary, several common and rare VWF missense variants contribute to phenotypic differences in VWF and FVIII among AAs.
Source: Blood
Authors: Jill M. Johnsen, Paul L. Auer, Alanna C. Morrison, Shuo Jiao, Peng Wei, Jeffrey Haessler, Keolu Fox, Sean R. McGee, Joshua D. Smith, Christopher S. Carlson, Nicholas Smith, Eric Boerwinkle, Charles Kooperberg, Deborah A. Nickerson, Stephen S. Rich, David Green, Ulrike Peters, Mary Cushman, Alex P. Reiner
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1078500014, G1186962729, Comprehensive Sequencing and Analysis of Variation in NHLBI Cohorts, G1275353700, G1726194250, G1947136479, Molecular Genetic Studies of von Willebrand Factor, G2273349799, G232440474, G233706301, G2412562481, ARRA - NHLBI Lung Cohorts Sequencing Project, G3545534745, G3550174423, CANDIDATE GENE ASSOCIATION RESOURCE (CARE), G388635167, G412187901, G5547620395, G5624510383, G587882820, G619791618, Human Exome Sequencing in Six Well-Phenotyped NHLBI Cohorts, G673128162, WHI Sequencing Project (WHISP), Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., G8536616440
OpenAlex ID: W2063071114