Genetic Predisposition of Both Waist Circumference and Hip Circumference Increased the Risk of Venous Thromboembolism

Thromb Haemost. 2023 Mar;123(3):347-361. doi: 10.1055/a-1980-8852. Epub 2022 Nov 16.

Abstract

Background: Obesity, especially abdominal obesity, is an independent indicator of increased cardiovascular risk. Observational studies have shown an observational association between obesity and venous thromboembolism (VTE). As a type of VTE, pulmonary embolism (PE) is also associated with obesity. However, it is unclear whether the observed associations are causal or caused by confounding bias or reverse causality.

Methods: We performed a two-sample test by obtaining the exposure dataset of waist circumference (WC) and hip circumference (HC) from the Neale Laboratory Consortium's genome-wide association study summary data and the summary-level outcome data of VTE and PE from FinnGen Biobank of European ancestry to determine the causal effect of WC and HC on VTE and PE.

Results: All three Mendelian randomization methods displayed a positive association between WC/HC and VTE/PE. WC and HC were positively associated with VTE (odds ratio [OR] = 1.803 per 1 standard deviation [SD] increase in WC, 95% confidence interval [CI] = 1.393-2.333; p < 0.001; OR = 1.479 per 1 SD increase in HC, 95% CI = 1.219-1.796; p < 0.001, respectively). Furthermore, we found a causal association between genetically predicted WC/HC and a higher risk of PE (OR = 1.929 per 1 SD increase in WC, 95% CI = 1.339-2.778, p < 0.001; OR = 1.431 per 1 SD increase in HC, 95% CI =1.095-1.869; p = 0.009, respectively).

Conclusion: There is a significant causal relationship between WC/HC and VTE/PE, which is consistent with observational studies. Taking measures to reduce WC/HC of obesity may help reduce the incidence of VTE/PE.

MeSH terms

  • Body Mass Index
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Obesity / complications
  • Obesity / epidemiology
  • Obesity / genetics
  • Risk Factors
  • Transcription Factors / genetics
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / epidemiology
  • Venous Thromboembolism* / genetics
  • Waist Circumference / genetics

Substances

  • Transcription Factors

Grants and funding

Funding This study and this research group were supported by grants from the Science and Technology Innovation Project of Jinan City (No. 201602153; No. 202019193), the Major Research and Development Project of Shandong Province (No. ZR2020MH041), the Natural Fund Project of Shandong Province (No. G201703080074), the project of the Central Government Guides Local Science and Technology Development (2021Szvup073), the National Natural Science Foundation of China (No. 81170274; No. 82170462), and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences (NCRC2020007).