Dataset Information

Associations Between Mean Platelet Volume and Risk of Deep Vein Thrombosis: A Mendelian Randomization Study and a Retrospective Study.

ABSTRACT:

Objective

In this study, it was intended to explore the causal association between mean platelet volume (MPV) and risk of deep vein thrombosis (DVT) using a two-sample Mendelian randomization (MR) analysis and a retrospective study.

Methods

This study applied two-sample MR analysis to estimate the causal association between MPV and risk of DVT. Twenty-one single nucleotide polymorphisms (SNPs) were selected as genetic variants from two independent consortiums cohorts (p-value <5×10^-8, linkage disequilibrium r²<0.1). Inverse variance weighted (IVW), MR-egger method and weighted median were performed. A retrospective study was also conducted to verify the associations identified from the MR study.

Results

The MR analysis demonstrated that genetically predicted higher MPV was associated with significantly lower risk of DVT (OR 0.982, 95% CI = 0.967-0.998, P = 0.023), with the consistent result in weighted median and MR-Egger. There was no directional horizontal pleiotropy in the method of MR-Egger regression (intercept=2.9e-04, P = 0.194). There was no single SNP was found to strongly drive the combined causal effect in the leave-one-out sensitivity analysis. Additionally, the similar result was observed in the retrospective study.

Conclusion

This study suggested that MPV was negatively associated with the risk of DVT. More basic researches are needed in the future to explore its specific mechanism.

SUBMITTER: Li J

PROVIDER: S-EPMC9922513 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Associations Between Mean Platelet Volume and Risk of Deep Vein Thrombosis: A Mendelian Randomization Study and a Retrospective Study.

Li Jianhong J Liang Yingna Y

International journal of general medicine 20230208

<h4>Objective</h4>In this study, it was intended to explore the causal association between mean platelet volume (MPV) and risk of deep vein thrombosis (DVT) using a two-sample Mendelian randomization (MR) analysis and a retrospective study.<h4>Methods</h4>This study applied two-sample MR analysis to estimate the causal association between MPV and risk of DVT. Twenty-one single nucleotide polymorphisms (SNPs) were selected as genetic variants from two independent consortiums cohorts (p-value <5×1 ...[more]

PMID: 36789132

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Project description:Deep vein thrombosis (DVT) is a serious condition characterized by blood clots in deep veins, posing a significant public health burden. Muscle strength has been implicated as a potential risk factor for DVT due to its influence on venous return. This study aims to investigate the causal association between muscle strength and DVT using a Mendelian randomization (MR) approach, leveraging genetic variants as instrumental variables (IVs). We conducted a 2-sample MR analysis using genome-wide association study (GWAS) data for hand-grip strength and DVT. IVs were selected based on their significant associations with muscle strength and DVT, as well as their linkage disequilibrium patterns. We employed statistical methods including inverse-variance weighting (IVW), MR-Egger, and weighted median to address pleiotropy bias. Sensitivity analyses were conducted to evaluate the robustness of the results. A total of 21 and 14 independent IVs were identified for hand grip strength (EWGSOP) and hand grip strength (FNIH), respectively. IVW analysis revealed a consistent causal and negative association between both definitions of hand grip strength and DVT (EWGSOP: OR = 0.702, 95% CI: 0.511-0.964, P = .029; FNIH: OR = 0.715, 95% CI: 0.570-0.898, P = .004). No directional pleiotropy was detected in MR-Egger and MR-PRESSO analyses for either definition (EWGSOP: MR-Egger Intercept P = .516; MR-PRESSO global test P = .162; FNIH: MR-Egger Intercept P = .569; MR-PRESSO global test P = .371).Sensitivity analyses demonstrated the stability of the causal effect estimates, with little influence from individual IVs. The MR analysis provided evidence of a causal association between muscle strength and DVT risk, suggesting that increasing muscle strength may have a protective effect. These findings have implications for preventive strategies and the promotion of resistance exercises and muscle-strengthening activities. Further research and validation of these results could inform clinical guidelines and interventions for DVT prevention.

Project description:ObjectiveTo investigate the genetic underpinnings of the association between type 2 diabetes (T2D), glycemic indicators such as fasting glucose (FG), fasting insulin (FI), and glycated hemoglobin (GH), and venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), thereby contributing novel insights to the scholarly discourse within this domain.MethodsGenome-wide association study (GWAS) summary data pertaining to exposures (T2D, FG, FI, GH) and outcomes (VTE, DVT, PE) were acquired from the IEU Open GWAS database, encompassing participants of European descent, including both male and female individuals. Two-sample Mendelian randomization (MR) analyses were conducted utilizing the TwoSampleMR and MRPRESSO packages within the R programming environment. The primary analytical approach employed was the random-effects inverse variance weighted (IVW) method. Heterogeneity was assessed via Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger. Horizontal pleiotropy was evaluated using the intercept test of MR Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, with the latter also employed for outlier detection. Additionally, a "Leave one out" analysis was conducted to ascertain the influence of individual single nucleotide polymorphisms (SNPs) on MR results.ResultsThe random-effects IVW analysis revealed a negative genetic causal association between T2D) and VTE (P = 0.008, Odds Ratio [OR] 95% confidence interval [CI] = 0.896 [0.827-0.972]), as well as between FG and VTE (P = 0.002, OR 95% CI = 0.655 [0.503-0.853]), GH and VTE (P = 0.010, OR 95% CI = 0.604 [0.412-0.884]), and GH and DVT (P = 0.002, OR 95% CI = 0.413 [0.235-0.725]). Conversely, the random-effects IVW analysis did not detect a genetic causal relationship between FI and VTE (P > 0.05), nor between T2D, FG, or FI and DVT (P > 0.05), or between T2D, FG, FI, or GH and PE (P > 0.05). Both the Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger indicated no significant heterogeneity (P > 0.05). Moreover, the intercept tests of MR Egger and MR-PRESSO suggested the absence of horizontal pleiotropy (P > 0.05). MR-PRESSO analysis identified no outliers, while the "Leave one out" analysis underscored that the MR analysis was not influenced by any single SNP.ConclusionOur investigation revealed that T2D, FG, and GH exhibit negative genetic causal relationships with VTE at the genetic level, while GH demonstrates a negative genetic causal relationship with DVT at the genetic level. These findings furnish genetic-level evidence warranting further examination of VTE, DVT, and PE, thereby making a contribution to the advancement of related research domains.

Project description:IntroductionSepsis is a public health problem due to its high prevalence and mortality. Mean platelet volume (MPV), a biomarker reported in routine blood counts, has been investigated and shows promise for determining fatal outcomes in septic patients.ObjectiveEvaluate whether the mean platelet volume (MPV) and mean platelet volume-to-platelet count (MPV/P) ratio are predictors of clinical severity and mortality in patients with sepsis.MethodsA prospective population cohort of 163 patients aged 18-97 years was recruited at the Intensive Care Unit of Pablo Arturo Hospital, Quito, Ecuador from 2017-2019 and followed up for 28 days. Patients were diagnosed with sepsis based on SEPSIS-3 septic shock criteria; in which the MPV and the MPV/P ratio were measured on days 1, 2, and 3. Sequential organ failure assessment (SOFA) score and presence of septic shock assessed clinical severity. Mortality on day 28 was considered the fatal outcome.ResultsThe average age of the patients was 61,15 years (SD 20,94) and female sex was predominant. MPV cutoff points at days 1, 2 and 3 were >9,45fL, >8,95fL and >8, 85fL; and (MPV/P) ratio >8, 18, >4, 12 y >3, 95, respectively. MPV at days 2 (9,85fL) and 3 (8,55fL) and (MPV/P) ratio at days 1 (4,42), 2 (4,21), and 3 (8,55), were predictors of clinical severity assessed by septic shock, which reached significance in the ROC curves. MPV and (MPV/P) ratio were also predictors of clinical severity determined by SOFA at days 1, 2, and 3, where higher values were observed in non-survivors reaching significance in all categories. MPV and MPV/P ratio at days 1, 2 and 3 were independent predictor factors of mortality using Cox proportional hazards model (HR 2,31; 95% CI 1,36-3,94), (HR 2,11; 95% CI 1,17-3,82), (HR 2,13; 95% CI 1,07-4,21) and (HR 2,38; 95% CI 1,38-4,12), (HR 2,15; 95% CI 1,14-4,06), (HR 4,43; 95% CI, 1,72-11,37) respectively.ConclusionsMPV and the MPV/P ratio are predictors of clinical severity and mortality in sepsis. The MPV and its coefficient are indicators of the biological behavior of platelets in sepsis. They should be considered as a cost-effective and rapidly available tool that guides the treatment.

Dataset Information

Associations Between Mean Platelet Volume and Risk of Deep Vein Thrombosis: A Mendelian Randomization Study and a Retrospective Study.

Objective

Methods

Results

Conclusion

Publications

Associations Between Mean Platelet Volume and Risk of Deep Vein Thrombosis: A Mendelian Randomization Study and a Retrospective Study.

Similar Datasets

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