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

12 Citations (Scopus)

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

Fingerprint

Venous Thromboembolism
African Americans
Polymorphism
Bioinformatics
Chromosomes
Gene expression
Logistics
Blood
Nucleotides
Genes
Chromosomes, Human, Pair 20
Population
Messenger RNA
Quantitative Trait Loci
Genome-Wide Association Study
Computational Biology
Ethnic Groups
Single Nucleotide Polymorphism
Logistic Models
Gene Expression

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hernandez, W., Gamazon, E. R., Smithberger, E., O'Brien, T. J., Harralson, A. F., Tuck, M., ... 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

Novel genetic predictors of venous thromboembolism risk in African Americans. / Hernandez, Wenndy; Gamazon, Eric R.; Smithberger, Erin; O'Brien, Travis J.; Harralson, Arthur F.; Tuck, Matthew; Barbour, April; Kittles, Rick A; Cavallari, Larisa H.; Perera, Minoli A.

In: Blood, Vol. 127, No. 15, 14.04.2016, p. 1923-1929.

Research output: Contribution to journalArticle

Hernandez, W, Gamazon, ER, Smithberger, E, O'Brien, TJ, Harralson, AF, Tuck, M, Barbour, A, Kittles, RA, Cavallari, LH & Perera, MA 2016, 'Novel genetic predictors of venous thromboembolism risk in African Americans', Blood, vol. 127, no. 15, pp. 1923-1929. https://doi.org/10.1182/blood-2015-09-668525
Hernandez W, Gamazon ER, Smithberger E, O'Brien TJ, Harralson AF, Tuck M et al. Novel genetic predictors of venous thromboembolism risk in African Americans. Blood. 2016 Apr 14;127(15):1923-1929. https://doi.org/10.1182/blood-2015-09-668525
Hernandez, Wenndy ; Gamazon, Eric R. ; Smithberger, Erin ; O'Brien, Travis J. ; Harralson, Arthur F. ; Tuck, Matthew ; Barbour, April ; Kittles, Rick A ; Cavallari, Larisa H. ; Perera, Minoli A. / Novel genetic predictors of venous thromboembolism risk in African Americans. In: Blood. 2016 ; Vol. 127, No. 15. pp. 1923-1929.
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