{"doi":"10.17615/vfwm-3q39","title":"Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans: Genetic associations for FVIII:C and VWF:ag","abstract":"Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, P=5.10 × 10−7 in EAs and P=3.88 × 10−3 in AAs) and VWF rs7962217 (Gly2705Arg, P=6.30 × 10−9 in EAs and P=2.98 × 10−2 in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P=8.02 × 10−10), with VWF rs1800380 in AAs (P=5.62 × 10−11), and with MAT1A rs2236568 in AAs (P=1.69 × 10−6). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs.","journal":"UNC Libraries","year":2020,"id":136627,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":245397,"name":"Aaron R. Folsom","orcid":"0000-0003-2635-2699","position":1,"is_corresponding":false},{"id":235848,"name":"James G. Wilson","orcid":"0000-0002-2676-8793","position":2,"is_corresponding":false},{"id":51219,"name":"Mary Cushman","orcid":"0000-0002-7871-6143","position":3,"is_corresponding":false},{"id":32869,"name":"Taylor Young","orcid":"0000-0003-3796-7322","position":4,"is_corresponding":false},{"id":437848,"name":"Qiong Yang","orcid":"0000-0002-4510-735X","position":5,"is_corresponding":false},{"id":25010,"name":"Alex P. Reiner","orcid":"0000-0002-1427-4470","position":6,"is_corresponding":false},{"id":515141,"name":"Leslie A. Lange","orcid":"0000-0002-8077-4975","position":7,"is_corresponding":false},{"id":25028,"name":"Russell P. Tracy","orcid":"0000-0002-0080-2420","position":8,"is_corresponding":false},{"id":90109,"name":"Herman A. Taylor","orcid":"0000-0003-3623-7264","position":9,"is_corresponding":false},{"id":414002,"name":"Weihong Tang","orcid":"0000-0003-1200-0270","position":10,"is_corresponding":false},{"id":25001,"name":"James S. Pankow","orcid":"0000-0001-7076-483X","position":11,"is_corresponding":false},{"id":25020,"name":"Nicholas L. Smith","orcid":"0000-0003-3483-353X","position":12,"is_corresponding":false},{"id":65159,"name":"DAVID R. JACOBS","orcid":"0000-0002-7232-0543","position":13,"is_corresponding":false},{"id":596337,"name":"Palmer, Cameron D.","orcid":null,"position":14,"is_corresponding":false},{"id":411540,"name":"Joseph A. Delaney","orcid":"0000-0003-1771-1776","position":15,"is_corresponding":false},{"id":595794,"name":"David Green","orcid":"0009-0004-9572-9853","position":16,"is_corresponding":false},{"id":596338,"name":"Lu Chen Weng","orcid":null,"position":17,"is_corresponding":false},{"id":49827,"name":"Brendan J. Keating","orcid":"0000-0002-3320-3723","position":18,"is_corresponding":false},{"id":27389,"name":"Christopher J. O’Donnell","orcid":"0000-0002-2667-8624","position":19,"is_corresponding":false},{"id":11274,"name":"Stephen S. 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