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dc.contributor.authorFrischmuth, Tobias
dc.contributor.authorHindberg, Kristian
dc.contributor.authorGabrielsen, Maiken Elvestad
dc.contributor.authorBrumpton, Ben Michael
dc.contributor.authorHveem, Kristian
dc.contributor.authorBrækkan, Sigrid Kufaas
dc.contributor.authorHansen, John-Bjarne
dc.contributor.authorMorelli, Vania Maris
dc.date.accessioned2022-03-16T09:08:25Z
dc.date.available2022-03-16T09:08:25Z
dc.date.issued2021-05-03
dc.description.abstract<p><b>Background</b> The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear. <p><b>Objective</b> 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. <p><b>Methods</b> Cases with incident VTE (<i> n</i>= 1,470) and a subcohort (<i> n</i> = 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). <p><b>Results</b> The combination of obesity (BMI ≥ 30kg/m<sup>2</sup>) 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/m<sup>2</sup> 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. <p><b>Conclusion</b> 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.en_US
dc.identifier.citationFrischmuth, Hindberg, Gabrielsen, Brumpton, Hveem, Brækkan, Hansen, Morelli. Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism. Thrombosis and Haemostasis. 2021en_US
dc.identifier.cristinIDFRIDAID 1924446
dc.identifier.doi10.1055/a-1497-9777
dc.identifier.issn0340-6245
dc.identifier.urihttps://hdl.handle.net/10037/24422
dc.language.isoengen_US
dc.publisherThieme Gruppeen_US
dc.relation.ispartofFrischmuth, T. (2023). Obesity-related venous thromboembolism. (Doctoral thesis). <a href=https://hdl.handle.net/10037/28520>https://hdl.handle.net/10037/28520</a>.
dc.relation.journalThrombosis and Haemostasis
dc.relation.projectIDStiftelsen Kristian Gerhard Jebsen: SKGJ-MED-015en_US
dc.relation.projectIDNorges forskningsråd: 248817en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holder© 2021. Thiemeen_US
dc.titleJoint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolismen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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