title: A genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups.
abstract: BACKGROUND
  D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.
  
  
  METHODS
  We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.
  
  
  RESULTS
  Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p<2.0×10(-6). The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p=0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p=0.006). No additional SNPs were significantly associated with D-dimer.
  
  
  CONCLUSIONS
  Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lu-Chen
authors.initials: LC
authors.lastname: Weng
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: tang0097@umn.edu.
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Public Health Sciences and the Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA; Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Saonli
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Delaney
authors.affiliation: Departments of Pathology and Biochemistry, University of Vermont, Burlington, VT, USA.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
authors.forename: Cameron D
authors.initials: CD
authors.lastname: Palmer
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Young
authors.affiliation: The NHLBI's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: Departments of Medicine and Pathology, University of Vermont, Burlington, VT, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005340:Fibrinogen / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C095381:factor V Leiden; C036309:fibrin fragment D; D005165:Factor V; D005340:Fibrinogen
keywords: CARe consortium; D-dimer; genetic association study; single nucleotide polymorphisms