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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

Marta Crous-Bou
1   Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
2   Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
,
Immaculata De Vivo
1   Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
2   Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
,
Carlos A. Camargo Jr
1   Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
2   Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
3   Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
,
Raphaëlle Varraso
4   INSERM U1168, VIMA (Aging and chronic diseases. Epidemiological and public health approaches), Villejuif, France
5   UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, France
,
Francine Grodstein
1   Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
2   Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
,
Majken K. Jensen
1   Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
6   Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
,
Peter Kraft
2   Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
7   Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
,
Samuel Z. Goldhaber
8   Cardiovascular Medicine Division, Department of Medicine, Brigham and Women’s, Boston, Massachusetts, USA
9   Harvard Medical School, Boston, Massachusetts, USA
,
Sara Lindström
2   Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
,
Christopher Kabrhel
3   Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
9   Harvard Medical School, Boston, Massachusetts, USA
› Author Affiliations Financial support: The Nurses’ Health Study, Nurses’ Health Study II and Health Professionals Follow up Study are supported by the National Cancer Institute – National Institutes of Health (UM1 CA186107, R01 CA49449, R01 HL034594, UM1 CA176726, R01 CA67262, UM1 CA167552, R01 HL35464). The genotyping on the NHS/NHSII/HPFS received grant supports from the National Institutes of Health (P01CA87969, R01CA49449, R01HL034594, R01HL088521, R01CA50385, R01CA67262, P01CA055075, R01HL35464, R01HL116854, HL34594, CA87969, HL35464, and CA55075) and by an unrestricted grant from Merck Research Laboratories, North Wales.
Further Information

Publication History

Received: 01 March 2016

Accepted after minor revision: 14 May 2016

Publication Date:
02 December 2017 (online)

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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

 

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