Major Genetic Susceptibility for Venous Thromboembolism in Men: A Study of Danish Twins

Larsen, Torben Bjerregaard; Sørensen, Henrik Toft; Skytthe, Axel; Johnsen, Søren Paaske; Vaupel, James W.; Christensen, Kaare

doi:10.1097/01.ede.0000060457.51194.bc

Cited by 109 publications

(79 citation statements)

References 32 publications

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“…4,5 Twin and family studies among populations of EA suggest that genetic factors explain up to 60% of VTE heritability. 8,9 Genome-wide association studies (GWASs) in populations of EA have confirmed the 2 well-established risk variants, factor V Leiden (rs6025) and prothrombin G20210A (rs1799963), and have identified several singlenucleotide polymorphisms (SNPs) in the ABO blood group gene (ABO) as susceptibility loci. [10][11][12] However, these variants are found in higher frequencies among individuals of EA compared with AAs, particularly rs6025 and rs1799963 which are nearly absent in AAs.…”

Section: Introductionmentioning

confidence: 99%

Novel genetic predictors of venous thromboembolism risk in African Americans

Hernandez

Gamazon

Smithberger

et al. 2016

Blood

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• Our study has identified common genetic risk factors for VTE among AAs.• These risk factors are associated with decreased thrombomodulin gene expression, suggesting a mechanistic link.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 risk of 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 3 10 27). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P 5 9.87 3 10 26 ). 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. (Blood. 2016;127(15):1923-1929

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Section: Introductionmentioning

confidence: 99%

Novel genetic predictors of venous thromboembolism risk in African Americans

Hernandez

Gamazon

Smithberger

et al. 2016

Blood

View full text Add to dashboard Cite

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“…12,13 In the last two decades, knowledge in this field has expanded and several single nucleotide polymorphisms have been identified that, if present, can affect an individual's risk of VTE. 14 These polymorphisms are single base-pair variations that have the potential to alter the function (e.g.…”

Section: Introductionmentioning

confidence: 99%

Joint effects of cancer and variants in the factor 5 gene on the risk of venous thromboembolism

et al. 2016

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“…Although certain risk factors have been identified, DVT is mainly caused by acquired factors including age, hospitalization, pregnancy, hormone therapy, cancer and surgery, and genetic risk factors including mutations and SNPs present in the genes actively involved in drug transport and metabolism. A number of various family and twin studies have revealed that genetic factors account for more than 60% of the risk for developing DVT (26,27). Regardless of ideal traditional treatment strategies with anticoagulants, a post-thrombotic syndrome often develops in one in four patients within a year while DVT recurs in one-third of patients within five years (28,29).…”

Section: Discussionmentioning

confidence: 99%