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Updated: Nov 7, 2025

A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis
Published on: June 2, 2015
Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism
Tobias Frischmuth1, Kristian Hindberg1, Maiken E Gabrielsen2
1Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway.
Background:
The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.
Objective:
To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case-cohort.
Methods:
Cases with incident VTE (n = 1,470) and a subcohort (n = 12,826) were derived from the Tromsø Study (1994-2012) and the Trøndelag Health Study (HUNT) (1995-2008). Participants were genotyped for ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865), and F11 (rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0-1, 2, 3, ≥4 alleles).
Results:
The combination of obesity (BMI ≥ 30kg/m2) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e., no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence interval [CI]: 2.05-3.96) increased risk of overall VTE compared with those with BMI <25 kg/m2 and 0 to 1 risk allele. However, in subgroups, the combination of obesity and ≥4 risk alleles was more pronounced for deep vein thrombosis (DVT) (HR: 3.20; 95% CI: 2.09-4.90) and unprovoked VTE (HR: 3.82; 95% CI: 2.25-6.47), suggesting a supra-additive effect.
Conclusion:
Our findings indicate that the combination of obesity and GRS has an additive effect on the risk of overall VTE. However, it may have a supra-additive effect on the risk of DVT and unprovoked VTE.
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