Download PDF
Thromb Haemost 2022; 122(09): 1549-1557
DOI: 10.1055/s-0042-1744377
Stroke, Systemic or Venous Thromboembolism

Association of Combined Lifestyle and Polygenetic Risk with Incidence of Venous Thromboembolism: A Large Population-Based Cohort Study

Yu-Jie Zhang
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
,
Zhi-Hao Li
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
,
Dong Shen
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
,
Pei-Dong Zhang
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
,
Shi-Hui Fu
2   Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China
,
Yao Yao
3   China Center for Health Development Studies, Peking University, Beijing, China
,
Jing-Xin Wang
4   Department of Rehabilitation, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China
,
Pei-Liang Chen
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
,
Pei Zhang
5   School of Life Science, Beijing Institute of Technology, Beijing, China
,
Xi-Ru Zhang
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
,
Chen Mao
1   Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (81973109 and 82173588 to C.M., 82001476 to Y-.J.Z.), China Postdoctoral Science Foundation (2020M682816 and 2021T140298 to Y-.J.Z.), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2019 to C.M.), the National Key Research and Development Program of China (2018YFC2000400 to C.M.), the Construction of High-level University of Guangdong (G820332010, G618339167, and G618339164 to C.M.), Guangdong Basic and Applied Basic Research Foundation (2021A1515011629T (C.M.), and Guangzhou Science and Technology Project (202002030255 to C.M.).
› Further Information
    Permissions and Reprints

Abstract

As one of the fatal complications, venous thromboembolism (VTE) is associated with increased mortality. However, the combined effects of adopting multiple healthy lifestyles have not been firmly demonstrated. This study was to evaluate the association of combined healthy lifestyles and genetic risk factors with VTE and to investigate their interaction. A prospective cohort study from UK Biobank with a total of 442,963 men and women aged between 38 to 73 years were recruited from 2006 to 2010 and followed up through 2017 or 2018. A polygenic risk score was constructed and a weighted healthy lifestyle score, including no current smoking, regular physical exercises, healthy diet, and healthy body mass index, was categorized. During a median follow-up 9.0 years (3,912,396 person-years), there were 6,736 (172 per 100,000 person-years) incident VTE cases recorded. Among the participants with an unfavorable lifestyle, 1.80% developed VTE, versus 1.03% of the participants with a favorable lifestyle (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.48–1.68). Of the participants with high genetic risk, 2.42% developed VTE, versus 0.97% of the participants with low genetic risk (HR: 2.60; 95% CI: 2.39–2.81). Moreover, of the participants with high genetic risk and unfavorable lifestyle, 2.90% developed VTE, versus 0.66% of the participants with low genetic risk and favorable lifestyle (HR: 4.09; 95% CI: 3.48–4.79). No significant interaction between genetic risk and lifestyle factors was observed (p for interaction = 0.727). An unfavorable lifestyle was associated with a substantially higher risk of VTE, regardless of the genetic risk strata.

Keywords

combined lifestyle - polygenetic risk - venous thromboembolism

Author Contributions

Y-.J.Z. contributed to the conception of the study design and drafted the manuscript. P-.D.Z. and P.Z. helped with the interpretation of data and the statistical analysis. Z-.H.L., D.S., S-.H.F., Y.Y., J-.X.W., P-.L.C., and X-.R.Z. helped with the revision of the manuscript. C.M. participated in the design of the study and was the guarantor of the work. All authors read and approved the final manuscript.


Data Availability

The UK Biobank data are available from the UK Biobank on request (www.ukbiobank.ac.uk/).


Supplementary Material



Publication History

Received: 12 January 2022

Accepted: 24 January 2022

Article published online:
27 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012; 379 (9828): 1835-1846
    CrossrefPubMedGoogle Scholar
  • 2 Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet 2016; 388 (10063): 3060-3073
    CrossrefPubMedGoogle Scholar
  • 3 Barco S, Valerio L, Ageno W. et al. Age-sex specific pulmonary embolism-related mortality in the USA and Canada, 2000–18: an analysis of the WHO Mortality Database and of the CDC Multiple Cause of Death database. Lancet Respir Med 2021; 9 (01) 33-42
    CrossrefPubMedGoogle Scholar
  • 4 Lowe GD. Common risk factors for both arterial and venous thrombosis. Br J Haematol 2008; 140 (05) 488-495
    CrossrefPubMedGoogle Scholar
  • 5 Severinsen MT, Overvad K, Johnsen S. et al. Genetic susceptibility, smoking, obesity and risk of venous thromboembolism. Br J Haematol 2010; 149 (02) 273-279
    CrossrefPubMedGoogle Scholar
  • 6 Trégouët DA, Health S, Saut N. et al. Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach. Blood 2009; 113 (21) 5298-5303
    CrossrefPubMedGoogle Scholar
  • 7 Lindström S, Wang L, Smith EN. et al. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. Blood 2019; 134 (19) 1645-1657
    CrossrefPubMedGoogle Scholar
  • 8 Klarin D, Busenkell E, Judy R. et al. Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease. Nat Genet 2019; 51 (11) 1574-1579
    CrossrefPubMedGoogle Scholar
  • 9 Gregson J, Kaptoge S, Bolton T. et al. Cardiovascular risk factors associated with venous thromboembolism. JAMA Cardiol 2019; 4 (02) 163-173
    CrossrefPubMedGoogle Scholar
  • 10 Steffen LM, Folsom AR, Cushman M. et al. Greater fish, fruit, and vegetable intakes are related to lower incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology. Circulation 2007; 115 (02) 188-195
    CrossrefPubMedGoogle Scholar
  • 11 Goldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol 2010; 56 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 12 Sudlow C, Gallacher J, Allen N. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 2015; 12 (03) e1001779
    CrossrefPubMedGoogle Scholar
  • 13 Li ZH, Gao X, Chung VC. et al. Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study. Ann Rheum Dis 2017; 79 (06) 829-836
    CrossrefPubMedGoogle Scholar
  • 14 Palmer LJ. UK Biobank: bank on it. Lancet 2007; 369 (9578): 1980-1982
    CrossrefPubMedGoogle Scholar
  • 15 Bycroft C, Freeman C, Petkova D. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 2018; 562 (7726): 203
    CrossrefPubMedGoogle Scholar
  • 16 Biobank UK. UK Biobank ethics and governance framework. . Accessed March 10, 2022 at: https://www.ukbiobank.ac.uk/media/0xsbmfmw/egf.pdf
    PubMedGoogle Scholar
  • 17 Lloyd-Jones DM, Hong Y, Labarthe D. , et al American Heart Association Strategic Planning Task Force and Statistics Committee. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's Strategic Impact Goal through 2020 and beyond. Circulation 2010; 121 (04) 586-613
    CrossrefPubMedGoogle Scholar
  • 18 Said MA, Verweij N, Harst P. et al. Associations of combined genetic and lifestyle risks with incident cardiovascular disease and diabetes in the UK Biobank study. JAMA Cardiol 2018; 3 (08) 693-702
    CrossrefPubMedGoogle Scholar
  • 19 Li YP, Pan A, Wang DD. et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation 2018; 138 (04) 345-355
    CrossrefPubMedGoogle Scholar
  • 20 Rutten-Jacobs LC, Larsson SC, Malik R. et al. Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants. BMJ 2018; 363: k4168
    CrossrefPubMedGoogle Scholar
  • 21 Lourida I, Hannon E, Littlejohns TJ. Association of lifestyle and genetic risk with incidence of dementia. JAMA 2019; 322 (05) 430-437
    CrossrefPubMedGoogle Scholar
  • 22 Crous-Bou M, Vivo ID, Jr CAC. et al. Interactions of established risk factors and a GWAS-based genetic risk score on the risk of venous thromboembolism. Thromb Haemost 2016; 116 (04) 705-713
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 de Hann HG, Bezemer ID, Doggen CJ. et al. Multiple SNP testing improves risk prediction of first venous thrombosis. Blood 2012; 120 (03) 656-663
    CrossrefPubMedGoogle Scholar
  • 24 Khera AV, Emdin CA, Drake I. et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med 2016; 375 (24) 2349-2358
    PubMedGoogle Scholar
  • 25 Klarin D, Emdin CA, Natarajan P. et al. Genetic analysis of venous thromboembolism in UK Biobank identifies the ZFPM2 locus and implicates obesity as a causal risk factor. Circ Cardiovasc Genet 2017; 10 (02) e001643
    CrossrefPubMedGoogle Scholar
  • 26 Townsend P. Deprivation. J Soc Policy 1987; 16 (02) 125-146
    CrossrefPubMedGoogle Scholar
  • 27 White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med 2011; 30 (04) 377-399
    CrossrefPubMedGoogle Scholar
  • 28 Park SY, Freedman ND, Haiman CA. et al. Association of coffee consumption with total and cause-specific mortality among nonwhite populations. Ann Intern Med 2017; 167 (04) 228-235
    CrossrefPubMedGoogle Scholar
  • 29 Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 2010; 29 (09) 1037-1057
    CrossrefPubMedGoogle Scholar
  • 30 Zöller B, Svensson PJ, Dahlbäck B. et al. Genetic risk factors for venous thromboembolism. Expert Rev Hematol 2020; 13 (09) 971-981
    CrossrefPubMedGoogle Scholar
  • 31 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496-509
    CrossrefPubMedGoogle Scholar
  • 32 World Health Organization. Global health risks report: mortality and burden of disease attributable to selected major risks. Accessed December 6, 2021 at: https://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf
    PubMedGoogle Scholar
  • 33 Khera AV, Emdin CA, Drake I. et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med 2016; 375 (24) 2349-2358
    CrossrefPubMedGoogle Scholar
  • 34 Evans CR, Hong CP, Folsom AR. et al. Lifestyle moderates genetic risk of venous thromboembolism: the ARIC study. Arterioscler Thromb Vasc Biol 2020; 40 (11) 2756-2763
    CrossrefPubMedGoogle Scholar
  • 35 Heit JA, Armasu SM, Asmann YW. et al. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. J Thromb Haemost 2012; 10 (08) 1521-1531
    CrossrefPubMedGoogle Scholar
  • 36 Germain M, Chasman DI, Haan H. et al. Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. Am J Hum Genet 2015; 96 (04) 532-542
    CrossrefPubMedGoogle Scholar
  • 37 Hinds DA, Buil A, Ziemek D. et al. Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis. Hum Mol Genet 2016; 25 (09) 1867-1874
    CrossrefPubMedGoogle Scholar
  • 38 Byrnes JR, Wolberg AS. Red blood cells in thrombosis. Blood 2017; 130 (16) 1795-1799
    CrossrefPubMedGoogle Scholar
  • 39 Koupenova M, Clancy L, Corkrey HA. et al. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circ Res 2018; 122 (02) 337-351
    CrossrefPubMedGoogle Scholar
  • 40 Cushman M, O'Meara ES, Heckbert SR. et al. Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology. Thromb Res 2016; 144: 127-132
    CrossrefPubMedGoogle Scholar
  • 41 Johannesen CDL, Flachs EM, Ebbehøj NE. et al. Sedentary work and risk of venous thromboembolism. Scand J Work Environ Health 2020; 46 (01) 69-76
    CrossrefPubMedGoogle Scholar
  • 42 Fletcher GF, Ades PA, Kligfield P. et al. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation 2015; 85 (03) 534-548
    PubMedGoogle Scholar
  • 43 Mozaffarian D. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation 2016; 133 (02) 187-225
    CrossrefPubMedGoogle Scholar
  • 44 Lutsey PL, Virnig BA, Durham SB. et al. Correlates and consequences of venous thromboembolism: the Iowa Women's Health Study. Am J Public Health 2010; 100 (08) 1506-1513
    CrossrefPubMedGoogle Scholar