Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism

Abstract 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 polymo...

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Veröffentlicht in:Thrombosis and haemostasis 2022-02, Vol.122 (2), p.267-276
Hauptverfasser: Frischmuth, Tobias, Hindberg, Kristian, Gabrielsen, Maiken E., Brumpton, Ben, Hveem, Kristian, Brækkan, Sigrid K., Hansen, John-Bjarne, Morelli, Vânia M.
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Sprache:eng
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Zusammenfassung:Abstract 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/m 2 ) 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
ISSN:0340-6245
2567-689X
DOI:10.1055/a-1497-9777