Novel genetic predictors of venous thromboembolism risk in African Americans

Wenndy Hernandez, Eric R. Gamazon, Erin Smithberger, Travis J. O'Brien, Arthur F. Harralson, Matthew Tuck, April Barbour, Rick A Kittles, Larisa H. Cavallari, Minoli A. Perera

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the riskof VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single-nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P <6 × 10-7). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (-6). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease.

Original languageEnglish (US)
Pages (from-to)1923-1929
Number of pages7
JournalBlood
Volume127
Issue number15
DOIs
StatePublished - Apr 14 2016

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Hernandez, W., Gamazon, E. R., Smithberger, E., O'Brien, T. J., Harralson, A. F., Tuck, M., Barbour, A., Kittles, R. A., Cavallari, L. H., & Perera, M. A. (2016). Novel genetic predictors of venous thromboembolism risk in African Americans. Blood, 127(15), 1923-1929. https://doi.org/10.1182/blood-2015-09-668525