title: A genetic risk score comprising known venous thromboembolism loci is associated with chronic venous disease in a multi-ethnic cohort.
abstract: BACKGROUND
  Chronic venous disease is common and shares some risk factors with venous thromboembolism (VTE). Several genetic loci have been discovered and well-replicated for VTE in European descent populations. We examined associations of a genetic risk score (GRS), comprising known VTE loci, with chronic venous disease.
  
  
  METHODS
  The San Diego Population Study (SDPS) is a multi-ethnic cohort that evaluated 2404 men and women aged 29-91 from 1994 to 1998 for chronic venous disease. The current study includes 1447 participants genotyped for 33 variants in 22 established VTE risk loci. Using these variants, unweighted and weighted GRS were constructed. Logistic regression was used to examine associations with venous disease.
  
  
  RESULTS
  In non-Hispanic whites, African-Americans, Hispanics, and Asians, each standard deviation increment higher of the unweighted 33-SNP GRS was associated with a 1.45-fold (95% CI (1.26, 1.67)), 1.74-fold (1.18, 2.55), a 1.80-fold (1.30, 2.51), and 1.88-fold (1.30, 2.73) greater odds, respectively, for moderate plus severe disease. The difference in c-statistics was significant between a known venous risk factor model and a model adding the 33-SNP GRS for whites (p=0.008), African-Americans (0.03), and Hispanics (p=0.04), with marginal significance in Asians (p=0.06).
  
  
  CONCLUSIONS
  GRS comprising variants primarily from VTE findings in European descent populations were associated with chronic venous disease across all race/ethnic groups, and contributed significantly to prediction, indicating some level of generalizability to other race/ethnic groups. Future work should focus on more in depth examination of racial/ethnic group genetic architecture in relation to chronic venous disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Burlington, VT, United States. Electronic address: cwassel@med.uvm.edu.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Wassel
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Rasmussen-Torvik
authors.affiliation: Department of Mathematics and Statistics, University of Vermont, Burlington, VT, United States.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Callas
authors.affiliation: Department of Family Medicine and Public Health, University of California - San Diego, La Jolla, CA, United States.
authors.forename: Julie O
authors.initials: JO
authors.lastname: Denenberg
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Burlington, VT, United States.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Durda
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, United States.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, United States.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Department of Family Medicine and Public Health, University of California - San Diego, La Jolla, CA, United States.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Allison
authors.affiliation: Clinical Epidemiology, Leiden University Medical Center, Netherlands.
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.affiliation: Department of Family Medicine and Public Health, University of California - San Diego, La Jolla, CA, United States.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Criqui
authors.affiliation: Departments of Medicine and Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Burlington, VT, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D054556:Venous Thromboembolism / Q000208:ethnology / Q000235:genetics*
keywords: Chronic venous disease; Genetic risk score; Race/ethnicity; Single nucleotide polymorphisms; Venous thromboembolism