{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:05:44Z","timestamp":1761541544190},"reference-count":18,"publisher":"Georg Thieme Verlag KG","issue":"04","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2009&gt;\u20090.5% and have therefore been investigated for their association with the VWF level in previous GWAS. The remaining 22 variants with frequencies\u2009&lt;\u20090.5% are less likely to have been evaluated previously. PolyPhen2 classified 3 out of the 22 variants as probably or possibly damaging (two in STAB2 and one in STX2); the others were either synonymous or benign. No accumulation of low frequency (0.05\u20130.5%) or rare variants (&lt;0.05%) in the VWD population compared to the gnomAD (Genome Aggregation Database) population was detected. Thus, rare variants in these genes do not contribute to the low VWF levels observed in VWD patients.<\/jats:p>","DOI":"10.1055\/s-0040-1718885","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T23:39:27Z","timestamp":1604187567000},"page":"e322-e331","source":"Crossref","is-referenced-by-count":2,"title":["Common and Rare Variants in Genes Associated with von Willebrand Factor Level Variation: No Accumulation of Rare Variants in Swedish von Willebrand Disease Patients"],"prefix":"10.1055","volume":"04","author":[{"given":"Eric","family":"Manderstedt","sequence":"additional","affiliation":[{"name":"Department of Environmental Science and Bioscience, Kristianstad University, Kristianstad, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Lind-Halld\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Environmental Science and Bioscience, Kristianstad University, Kristianstad, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Lethagen","sequence":"additional","affiliation":[{"name":"Department for Coagulation Disorders, University Hospital, Malm\u00f6, Sweden"},{"name":"National Hemophilia Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark"},{"name":"Sobi, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christer","family":"Halld\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Environmental Science and Bioscience, Kristianstad University, Kristianstad, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"issue":"23","key":"ref1","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1182\/blood-2013-06-498303","article-title":"von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy","volume":"122","author":"D Lillicrap","year":"2013","journal-title":"Blood"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.blre.2016.08.003","article-title":"Genetic diagnosis in hemophilia and von Willebrand disease","volume":"31","author":"L L Swystun","year":"2017","journal-title":"Blood Rev"},{"issue":"12","key":"ref3","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1161\/CIRCULATIONAHA.109.869156","article-title":"Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: the CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium","volume":"121","author":"N L Smith","year":"2010","journal-title":"Circulation"},{"issue":"11","key":"ref4","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1182\/blood-2015-02-624551","article-title":"Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and 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mutations","volume":"10","author":"C Halld\u00e9n","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref11","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/ejhg.2015.222","article-title":"Genome-wide association studies identify genetic loci for low von Willebrand factor levels","volume":"24","author":"J van Loon","year":"2016","journal-title":"Eur J Hum Genet"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.blre.2010.03.003","article-title":"The genetic basis of von Willebrand disease","volume":"24","author":"A C Goodeve","year":"2010","journal-title":"Blood Rev"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"e0192024","DOI":"10.1371\/journal.pone.0192024","article-title":"Genetic variation in the C-type lectin receptor CLEC4M in type 1 von Willebrand disease patients","volume":"13","author":"E Manderstedt","year":"2018","journal-title":"PLoS 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