Dataset Information

Effect of handgrip on coronary artery disease and myocardial infarction: a Mendelian randomization study.

ABSTRACT: Observational studies have reported an association of handgrip strength with risk of cardiovascular disease. However, residual confounding and reverse causation may have influenced these findings. A Mendelian randomization (MR) study was conducted to examine whether handgrip is causally associated with cardiovascular disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were used as the genetic instruments for handgrip. The effect of each SNP on coronary artery disease/myocardial infarction (CAD/MI) was weighted by its effect on handgrip strength, and estimates were pooled to provide a summary measure for the effect of increased handgrip on risk of CAD/MI. MR analysis showed that higher grip strength reduces risk for CAD/MI, with 1-kilogram increase in genetically determined handgrip reduced odds of CAD by 6% (odds ratio (OR)?=?0.94, 95% confidence interval (CI) 0.91-0.99, P?=?0.01), and reduced odds of MI by 7% (OR?=?0.93, 95% CI 0.89-0.98, P?=?0.003). No association of grip strength with type 2 diabetes, body mass index, LDL- and HDL-cholesterol, triglycerides and fasting glucose was found. The inverse causal relationship between handgrip and the risk of CAD or MI suggests that promoting physical activity and resistance training to improve muscle strength may be important for cardiovascular health.

SUBMITTER: Xu L

PROVIDER: S-EPMC5430422 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Effect of handgrip on coronary artery disease and myocardial infarction: a Mendelian randomization study.

Xu Lin L Hao Yuan Tao YT

Scientific reports 20170419 1

Observational studies have reported an association of handgrip strength with risk of cardiovascular disease. However, residual confounding and reverse causation may have influenced these findings. A Mendelian randomization (MR) study was conducted to examine whether handgrip is causally associated with cardiovascular disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were used as the genetic instruments for handgrip. The effect of each SNP on coronary artery disease/myo ...[more]

PMID: 28424468

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Project description:Background: Previous studies have indicated that the gut microbiota (GM) is associated with coronary artery disease (CAD), but the causality of these associations remains unestablished due to confounding factors and reverse causality. We conducted Mendelian randomization study (MR) to determine the causal effect of the specific bacterial taxa on CAD/myocardial infarction (MI) and identify the mediating factors involved. Methods: Two-sample MR, multivariable MR (MVMR) and mediation analysis were performed. Inverse-variance weighting (IVW) was the main method used to analyze causality, and sensitivity analysis was used to verify the reliability of the study. Causal estimates from CARDIoGRAMplusC4D and FinnGen databases were combined using the meta-analysis method, and repeated validation was conducted based on the UK Biobank (UKB) database. Confounders that may affect the causal estimates were corrected by MVMP and the potential mediation effects were investigated by using mediation analysis. Results: The study suggested that increased abundance of the RuminococcusUCG010 genus leads to a lower risk of CAD (OR, 0.88; 95% CI, 0.78, 1.00; p = 2.88 × 10-2) and MI (OR, 0.88; 95% CI, 0.79, 0.97; p = 1.08 × 10-2), with consistent results in both meta-analysis (CAD: OR, 0.86; 95% CI, 0.78, 0.96; p = 4.71 × 10-3; MI: OR, 0.82; 95% CI, 0.73, 0.92; p = 8.25 × 10-4) and repeated analysis of the UKB dataset (CAD: OR, 0.99; 95% CI, 0.99, 1.00, p = 2.53 × 10-4; MI: OR, 0.99; 95% CI, 0.99, 1.00, p = 1.85 × 10-11). Based on multiple databases, T2DM was proved as a mediating factor in the causal effect of RuminococcusUCG010 and CAD/MI, with an average mediation effect proportion of 20% on CAD and 17% on MI, respectively. Conclusion: This MR study provided suggestive genetic evidence that the higher the RuminococcusUCG010 abundance is, the lower the risk of CAD and MI, with T2DM playing a mediating effect. This genus may become a novel target in strategies for treating and preventing CAD and MI.

Project description:BackgroundNumerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.MethodsFor the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.ResultsAfter adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261-12.432; P < 0.001; FDR-corrected P < 0.001) and MI (OR = 2.287; 95% CI 1.218-4.300; P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.ConclusionOur findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.

Dataset Information

Effect of handgrip on coronary artery disease and myocardial infarction: a Mendelian randomization study.

Publications

Effect of handgrip on coronary artery disease and myocardial infarction: a Mendelian randomization study.

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