Dataset Information

Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index: A Mendelian Randomization Study.

ABSTRACT: Owing to the susceptibility of conventional observational studies to confounding factors and reverse causation, the causal association between cardiac function and frailty is unclear. We aimed to investigate whether cardiac function has causal effects on frailty. In this study, a two-sample Mendelian randomization (MR) study was conducted using genetic variants associated with cardiac function assessed by magnetic resonance imaging phenotypes as instrumental variables. Genetic variants associated with cardiac function by magnetic resonance imaging (including seven cardiac function phenotypes) and the frailty index (FI) were obtained from two large genome-wide association studies. MR estimates from each genetic instrument were combined using inverse variance weighted (IVW), weighted median, and MR‒Egger regression methods. We found that the increase in genetically determined stroke volume (beta - 0.13, 95% CI - 0.16 to - 0.10, p = 1.39E-6), rather than other cardiac phenotypes, was associated with lower FI in MR analysis of IVW after Bonferroni correction. Sensitivity analyses examining potential bias caused by pleiotropy or reverse causality revealed similar findings (e.g., intercept [SE], - 0.008 [0.011], p = 0.47 by MR‒Egger intercept test). The leave-one-out analysis indicated that the association was not driven by single nucleotide polymorphisms. No evidence of heterogeneity was found among the genetic variants (e.g., MR‒Egger: Q statistic = 14.4, p = 0.156). In conclusion, we provided evidence that improved cardiac function could contribute to reducing FI. These findings support the hypothesis that enhancing cardiac function could be an effective prevention strategy for frailty.

Supplementary information

The online version contains supplementary material available at 10.1007/s43657-022-00072-z.

SUBMITTER: Zhang H

PROVIDER: S-EPMC9712899 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index: A Mendelian Randomization Study.

Zhang Hui H Hao Meng M Hu Zixin Z Li Yi Y Hu Xiaoxi X Jiang Xiaoyan X Liu Zuyun Z Sun Xuehui X Wang Xiaofeng X

Phenomics (Cham, Switzerland) 20220929 6

Owing to the susceptibility of conventional observational studies to confounding factors and reverse causation, the causal association between cardiac function and frailty is unclear. We aimed to investigate whether cardiac function has causal effects on frailty. In this study, a two-sample Mendelian randomization (MR) study was conducted using genetic variants associated with cardiac function assessed by magnetic resonance imaging phenotypes as instrumental variables. Genetic variants associate ...[more]

PMID: 36939795

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Project description:BackgroundFrailty index and vestibular disorders appear to be associated in observational studies, but causality of the association remains unclear.MethodsA two-sample Mendelian randomization (MR) study was implemented to explore the causal relationship between the frailty index and vestibular disorders in individuals of European descent. A genome-wide association study (GWAS) of frailty index was used as the exposure (n = 175, 226), whereas the GWAS of vestibular disorders was the outcome (n = 462,933). MR Steiger filtering method was conducted to investigate the causal effect of the frailty index on vestibular disorders. An inverse variance weighted (IVW) approach was used as the essential approach to examine the causality. Additionally, the MR-Egger methods, the simple mode analysis, the weighted median analysis, and the weighted mode analysis were used as supplementary methods. The MR-PRESSO analysis, the MR-Egger intercept analysis, and Cochran's Q statistical analysis also were used to detect the possible heterogeneity as well as directional pleiotropy. To evaluate this association, the odds ratio (OR) with 95% confidence intervals (CIs) was used. All statistical analyses were performed in R. The STROBE-MR checklist for the reporting of MR studies was used in this study.ResultsIn total, 14 single nucleotide polymorphisms (SNPs) were identified as effective instrumental variables (IVs) in the two sample MR analyses. The significant causal effect of the frailty index on vestibular disorders was demonstrated by IVW method [OR 1.008 (95% CI 1.003, 1.013), p = 0.001]. Results from the various sensitivity analysis were consistent. The "leave-one-out" analysis indicated that our results were robust even without a single SNP. According to the MR-Egger intercept test [intercept = -0.000151, SE = 0.011, p = 0.544], genetic pleiotropy did not affect the results. No heterogeneity was detected by Cochran's Q test. Results of MR Steiger directionality test indicated the accuracy of our estimate of the potential causal direction (Steiger p < 0.001).ConclusionThe MR study suggested that genetically predicted frailty index may be associated with an increased risk of vestibular disorders. Notably, considering the limitations of this study, the causal effects between frailty index and vestibular disorders need further investigation. These results support the importance of effectively managing frailty which may minimize vestibular disorders and improve the quality of life for those with vestibular disorders.

Project description:ObjectivesTo determine the test-retest reproducibility and observer variability of CMR-derived LA function, using (i) LA strain (LAS) and strain rate (LASR), and (ii) LA volumes (LAV) and emptying fraction (LAEF).MethodsSixty participants with and without cardiovascular disease (aortic stenosis (AS) (n = 16), type 2 diabetes (T2D) (n = 28), end-stage renal disease on haemodialysis (n = 10) and healthy volunteers (n = 6)) underwent two separate CMR scans 7-14 days apart. LAS and LASR, corresponding to LA reservoir, conduit and contractile booster-pump function, were assessed using Feature Tracking software (QStrain v2.0). LAEF was calculated using the biplane area length method (QMass v8.1). Both were assessed using 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values were calculated. Intra- and inter-observer variabilities were assessed in 10 randomly selected participants.ResultsThe test-retest reproducibility was moderate to poor for all strain and strain rate parameters. Overall, strain and strain rate corresponding to reservoir phase (LAS_r, LASR_r) were the most reproducible, yielding the smallest coefficient of variance (CoV) (29.9% for LAS_r, 28.9% for LASR_r). The test-retest reproducibility for LAVs and LAEF was good: LAVmax CoV = 19.6% ICC = 0.89, LAVmin CoV = 27.0% ICC = 0.89 and total LAEF CoV = 15.6% ICC = 0.78. The inter- and intra-observer variabilities were good for all parameters except for conduit function.ConclusionThe test-retest reproducibility of LA strain and strain rate assessment by CMR utilising Feature Tracking is moderate to poor across disease states, whereas LA volume and emptying fraction are more reproducible on CMR. Further improvements in LA strain quantification are needed before widespread clinical application.Key points• LA strain and strain rate assessment using Feature Tracking on CMR has moderate to poor test-retest reproducibility across disease states. • The test-retest reproducibility for the biplane method of assessing LA function is better than strain assessment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. • Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.

Project description:BackgroundFrailty is closely related to cancer. Previous research has shown that cancer patients are prone to frailty, and frailty increases the risk of adverse outcomes in cancer patients. However, it is unclear whether frailty increases the risk of cancer. This 2-sample Mendelian-randomization (MR) study sought to analyze the relationship between frailty and the risk of colon cancer.MethodsThe database was extracted from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) in 2021. The genome-wide association study (GWAS) data related to colon cancer was obtained from the GWAS website (http://gwas.mrcieu.ac.uk/datasets), involving 462,933 individuals' gene information. Single-nucleotide polymorphisms (SNPs) were defined as the instrumental variables (IVs). The SNPs closely associated with the Frailty Index at a genome-wide significance level were selected. To further screen the IVs, we selected the confounding factors using the PhenoScanner (http://www.phenoscanner.medschl.cam.ac.uk/phenoscanner). To estimate the causal effect of the Frailty Index on colon cancer, the MR-Egger regression, weighted median (WM1), inverse-variance weighted (IVW), and weight mode (WM2) methods were applied to calculate the SNP-frailty index and the SNP-cancer estimates. Cochran's Q statistic was used to estimate heterogeneity. The two-sample Mendelian randomization (TSMR) analysis was performed using the "TwoSampleMR" and "plyr" packages. All the statistical tests were 2-tailed, and a P value <0.05 was considered statistically significant.ResultsWe selected 8 SNPs as the IVs. The results of the IVW analysis [odds ratio (OR) =0.995, 95% confidence interval (CI): 0.990-1.001, P=0.052] showed that the genetic changes in the Frailty Index were not statistically associated with the risk of colon cancer, and no significant heterogeneity between these 8 genes was observed (Q =7.382, P=0.184). The MR-Egger (OR =0.987, 95% CI: 0.945-1.031, P=0.581), WM1 (OR =0.995, 95% CI: 0.990-1.001, P=0.118), WM2 (OR =0.996, 95% CI: 0.988-1.004, P=0.356), and SM (OR =0.996, 95% CI: 0.987-1.005, P=0.449) results were also consistent with each other. The sensitivity analysis based on the leave-one-out method showed that the individual SNPs did not affect the robustness of the results.ConclusionsFrailty might have no effect on the risk of colon cancer.

Dataset Information

Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index: A Mendelian Randomization Study.

Supplementary information

Publications

Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index: A Mendelian Randomization Study.

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