Taller height as a risk factor for venous thromboembolism

a Mendelian randomization meta-analysis

N. S. Roetker, S. M. Armasu, J. S. Pankow, P. L. Lutsey, W. Tang, M. A. Rosenberg, T. M. Palmer, R. F. MacLehose, S. R. Heckbert, M. Cushman, Mariza De Andrade, A. R. Folsom

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Essentials Observational data suggest taller people have a higher risk of venous thromboembolism (VTE). We used Mendelian randomization techniques to further explore this association in three studies. Risk of VTE increased by 30–40% for each 10 cm increment in height. Height was more strongly associated with deep vein thrombosis than with pulmonary embolism. Summary: Background Taller height is associated with a greater risk of venous thromboembolism (VTE). Objectives To use instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship. Methods Participants of European ancestry were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC] study and Cardiovascular Health Study [CHS]) and one case–control study (Mayo Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a previously published meta-analysis, and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10-cm increment in height. ORs were pooled across the three studies by the use of inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% confidence interval [CI] 1.11–1.46), 1.34 (95% CI 1.04–1.73) and 1.45 (95% CI 1.04–2.01) per 10-cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including taller people having a greater venous surface area, a higher number of venous valves, or greater hydrostatic pressure, need to be explored further.

Original languageEnglish (US)
Pages (from-to)1334-1343
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Mendelian Randomization Analysis
Venous Thromboembolism
Meta-Analysis
Odds Ratio
Confidence Intervals
Random Allocation
Single Nucleotide Polymorphism
Atherosclerosis
Venous Valves
Hydrostatic Pressure
Health
Pulmonary Embolism
Venous Thrombosis

Keywords

  • body height
  • genetics
  • Mendelian randomization analysis
  • meta-analysis
  • venous thromboembolism

ASJC Scopus subject areas

  • Hematology

Cite this

Roetker, N. S., Armasu, S. M., Pankow, J. S., Lutsey, P. L., Tang, W., Rosenberg, M. A., ... Folsom, A. R. (2017). Taller height as a risk factor for venous thromboembolism: a Mendelian randomization meta-analysis. Journal of Thrombosis and Haemostasis, 15(7), 1334-1343. https://doi.org/10.1111/jth.13719

Taller height as a risk factor for venous thromboembolism : a Mendelian randomization meta-analysis. / Roetker, N. S.; Armasu, S. M.; Pankow, J. S.; Lutsey, P. L.; Tang, W.; Rosenberg, M. A.; Palmer, T. M.; MacLehose, R. F.; Heckbert, S. R.; Cushman, M.; De Andrade, Mariza; Folsom, A. R.

In: Journal of Thrombosis and Haemostasis, Vol. 15, No. 7, 01.07.2017, p. 1334-1343.

Research output: Contribution to journalArticle

Roetker, NS, Armasu, SM, Pankow, JS, Lutsey, PL, Tang, W, Rosenberg, MA, Palmer, TM, MacLehose, RF, Heckbert, SR, Cushman, M, De Andrade, M & Folsom, AR 2017, 'Taller height as a risk factor for venous thromboembolism: a Mendelian randomization meta-analysis', Journal of Thrombosis and Haemostasis, vol. 15, no. 7, pp. 1334-1343. https://doi.org/10.1111/jth.13719
Roetker, N. S. ; Armasu, S. M. ; Pankow, J. S. ; Lutsey, P. L. ; Tang, W. ; Rosenberg, M. A. ; Palmer, T. M. ; MacLehose, R. F. ; Heckbert, S. R. ; Cushman, M. ; De Andrade, Mariza ; Folsom, A. R. / Taller height as a risk factor for venous thromboembolism : a Mendelian randomization meta-analysis. In: Journal of Thrombosis and Haemostasis. 2017 ; Vol. 15, No. 7. pp. 1334-1343.
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abstract = "Essentials Observational data suggest taller people have a higher risk of venous thromboembolism (VTE). We used Mendelian randomization techniques to further explore this association in three studies. Risk of VTE increased by 30–40{\%} for each 10 cm increment in height. Height was more strongly associated with deep vein thrombosis than with pulmonary embolism. Summary: Background Taller height is associated with a greater risk of venous thromboembolism (VTE). Objectives To use instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship. Methods Participants of European ancestry were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC] study and Cardiovascular Health Study [CHS]) and one case–control study (Mayo Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a previously published meta-analysis, and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10-cm increment in height. ORs were pooled across the three studies by the use of inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95{\%} confidence interval [CI] 1.11–1.46), 1.34 (95{\%} CI 1.04–1.73) and 1.45 (95{\%} CI 1.04–2.01) per 10-cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including taller people having a greater venous surface area, a higher number of venous valves, or greater hydrostatic pressure, need to be explored further.",
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T1 - Taller height as a risk factor for venous thromboembolism

T2 - a Mendelian randomization meta-analysis

AU - Roetker, N. S.

AU - Armasu, S. M.

AU - Pankow, J. S.

AU - Lutsey, P. L.

AU - Tang, W.

AU - Rosenberg, M. A.

AU - Palmer, T. M.

AU - MacLehose, R. F.

AU - Heckbert, S. R.

AU - Cushman, M.

AU - De Andrade, Mariza

AU - Folsom, A. R.

PY - 2017/7/1

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N2 - Essentials Observational data suggest taller people have a higher risk of venous thromboembolism (VTE). We used Mendelian randomization techniques to further explore this association in three studies. Risk of VTE increased by 30–40% for each 10 cm increment in height. Height was more strongly associated with deep vein thrombosis than with pulmonary embolism. Summary: Background Taller height is associated with a greater risk of venous thromboembolism (VTE). Objectives To use instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship. Methods Participants of European ancestry were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC] study and Cardiovascular Health Study [CHS]) and one case–control study (Mayo Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a previously published meta-analysis, and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10-cm increment in height. ORs were pooled across the three studies by the use of inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% confidence interval [CI] 1.11–1.46), 1.34 (95% CI 1.04–1.73) and 1.45 (95% CI 1.04–2.01) per 10-cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including taller people having a greater venous surface area, a higher number of venous valves, or greater hydrostatic pressure, need to be explored further.

AB - Essentials Observational data suggest taller people have a higher risk of venous thromboembolism (VTE). We used Mendelian randomization techniques to further explore this association in three studies. Risk of VTE increased by 30–40% for each 10 cm increment in height. Height was more strongly associated with deep vein thrombosis than with pulmonary embolism. Summary: Background Taller height is associated with a greater risk of venous thromboembolism (VTE). Objectives To use instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship. Methods Participants of European ancestry were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC] study and Cardiovascular Health Study [CHS]) and one case–control study (Mayo Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a previously published meta-analysis, and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10-cm increment in height. ORs were pooled across the three studies by the use of inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% confidence interval [CI] 1.11–1.46), 1.34 (95% CI 1.04–1.73) and 1.45 (95% CI 1.04–2.01) per 10-cm greater height, respectively. Conclusions Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including taller people having a greater venous surface area, a higher number of venous valves, or greater hydrostatic pressure, need to be explored further.

KW - body height

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