A genetic risk score comprising known venous thromboembolism loci is associated with chronic venous disease in a multi-ethnic cohort

Christina L. Wassel*, Laura J. Rasmussen-Torvik, Peter W. Callas, Julie O. Denenberg, J. Peter Durda, Alexander P. Reiner, Nicholas L. Smith, Matthew A. Allison, Frits R. Rosendaal, Michael H. Criqui, Mary Cushman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)966-973
Number of pages8
JournalThrombosis research
Volume136
Issue number5
DOIs
StatePublished - Nov 2015

Keywords

  • Chronic venous disease
  • Genetic risk score
  • Race/ethnicity
  • Single nucleotide polymorphisms
  • Venous thromboembolism

ASJC Scopus subject areas

  • Hematology

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