Dataset Information

Leisure sedentary behaviour increases the risk of venous thromboembolism: a Mendelian randomisation study.

ABSTRACT:

Background

Venous thromboembolism (VTE) is a substantial contributor to the global burden of disease. Observational studies have suggested that leisure sedentary behaviours (LSB) are related to the risk of VTE; however, the causal role of LSB in VTE remains unclear.

Methods

Using data obtained from genome-wide association studies in the UK Biobank (N = 422,218), we identified 84, 21, and 4 single nucleotide polymorphisms (SNPs) related to sedentary television (TV) watching, computer use, and driving, respectively. These SNPs were employed as instrumental variables. Summary statistics for SNP-VTE associations was obtained from the FinnGen study (5,403 cases and 130,235 controls). Two-sample Mendelian randomisation (MR) analyses were performed using inverse-variance weighted (IVW), MR-Egger,weighted median, and weighted mode approaches. Sensitivity analyses were conducted to ensure robustness of the results.

Results

The main IVW approach demonstrated a positive association between the genetically predicted sedentary TV watching and the risk of VTE [odds ratio (OR):1.35, 95% confidence interval (CI):1.02-1.80, P = 0.039]. However, no significant association was observed for genetically predicted sedentary computer use or driving and VTE risk. The results from our series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and MR-Pleiotropy RESidual Sum and Outlier method, further supported these findings.

Conclusion

This study provides evidence of an association between genetically predicted sedentary TV watching and the risk of VTE. Further studies are required to elucidate the underlying causal mechanisms.

SUBMITTER: Chen L

PROVIDER: S-EPMC10354998 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Leisure sedentary behaviour increases the risk of venous thromboembolism: a Mendelian randomisation study.

Chen Liang L You Guochang G Yang Zhenmei Z Shen Runnan R Zhang Rong R Zhu Dongxi D Wang Linlu L Lin Shen S Lv Lin L Huang Kai K

BMC cardiovascular disorders 20230718 1

<h4>Background</h4>Venous thromboembolism (VTE) is a substantial contributor to the global burden of disease. Observational studies have suggested that leisure sedentary behaviours (LSB) are related to the risk of VTE; however, the causal role of LSB in VTE remains unclear.<h4>Methods</h4>Using data obtained from genome-wide association studies in the UK Biobank (N = 422,218), we identified 84, 21, and 4 single nucleotide polymorphisms (SNPs) related to sedentary television (TV) watching, comput ...[more]

PMID: 37464328

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Project description:ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

Project description:BackgroundPrevious cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).MethodsWe used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.ResultsOur findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01-1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20-2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG's genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20-1.78) and in females (OR: 1.49, 95% CI: 1.17-1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08-1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01-1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.ConclusionOur study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

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Project description:BackgroundThe 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study.MethodsData were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators.ResultsGenetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88-0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29-1.88; P = 4.68 × 10-6) and disease severity (OR = 1.85, 95% CI 1.33-2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance and the occurrence of type 2 diabetes.ConclusionOur findings supported a causal effect of accelerometer-assessed PA on the reduced risk of COVID-19 hospitalization as well as television watching on the increased risk of COVID-19 hospitalization and severity, which was potentially mediated by smoking, obesity and type 2 diabetes-related phenotypes. Particular attention should be given to reducing leisure sedentary behaviors and encouraging proper exercise during isolation and quarantine for COVID-19.

Dataset Information

Leisure sedentary behaviour increases the risk of venous thromboembolism: a Mendelian randomisation study.

Background

Methods

Results

Conclusion

Publications

Leisure sedentary behaviour increases the risk of venous thromboembolism: a Mendelian randomisation study.

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