Interactions of established risk factors and a GWAS-based genetic risk score on the risk of venous thromboembolism

Marta Crous-Bou; Immaculata De Vivo; Carlos A. Camargo Jr; Raphaëlle Varraso; Francine Grodstein; Majken K. Jensen; Peter Kraft; Samuel Z. Goldhaber; Sara Lindström; Christopher Kabrhel

doi:10.1160/TH16-02-0172

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 116(04): 705-713
DOI: 10.1160/TH16-02-0172

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH

Interactions of established risk factors and a GWAS-based genetic risk score on the risk of venous thromboembolism

Authors

Marta Crous-Bou

¹Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

²Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Immaculata De Vivo

¹Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

²Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Carlos A. Camargo Jr

¹Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

²Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA

³Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
Raphaëlle Varraso

⁴INSERM U1168, VIMA (Aging and chronic diseases. Epidemiological and public health approaches), Villejuif, France

⁵UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, France
Francine Grodstein

¹Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

²Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Majken K. Jensen

¹Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

⁶Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Peter Kraft

²Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA

⁷Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Samuel Z. Goldhaber

⁸Cardiovascular Medicine Division, Department of Medicine, Brigham and Women’s, Boston, Massachusetts, USA

⁹Harvard Medical School, Boston, Massachusetts, USA
Sara Lindström

²Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
Christopher Kabrhel

³Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA

⁹Harvard Medical School, Boston, Massachusetts, USA

Abstract

Summary

Multiple genetic and environmental risk factors contribute to venous thromboembolism (VTE) risk. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of VTE and may identify opportunities for targeted prevention and treatment. It was our aim to examine the main effects and the potential effect-modification between single nucleotide polymorphisms (SNPs) at established loci and lifestyle risk factors for VTE. We performed a nested case-control study using data on 1,040 incident VTE cases and 16,936 controls from the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood, were selected as participants in a previous genome-wide association study (GWAS), and completed a biennial questionnaire at time of blood draw. We selected SNPs that were associated with VTE risk in previous GWAS studies. A genetic risk score (GRS) was constructed to evaluate the combined effect of the 16 SNPs that have reached genome-wide significance in previous GWAS of VTE. Interactions between SNPs and VTE risk factors (BMI and smoking) were also assessed. We found a significant association between our GRS and VTE risk. The risk of VTE among individuals in the highest GRS tertile was 2.02 times that of individuals in the lowest GRS tertile (p-trend = 9.69x10^-19). The OR was 1.52 (p=1.03x10^-8) for participants in the highest GRS tertile compared to those in the medium GRS tertile. However, while BMI and smoking were associated with VTE, and their effects were additive to each other we did not observe any significant multiplicative gene-environment interactions.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Body mass index - smoking - genetic susceptibility - gene-environment interactions - venous thromboembolism

Full Text

References

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Supplementary Material

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