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.
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Data Availability
The full GWAS summary statistics of cardiac function by MRI from the main analysis for each of the seven traits are available for download from the Broad Institute Cardiovascular Disease Knowledge Portal under the ‘Downloads’ (http://www.broadcvdi.org/). Full GWAS summary statistics of gene-frailty index are freely available for download via the GWAS catalogue (https://www.ebi.ac.uk/gwas/downloads/summary-statistics; study accession GCST90020053) or directly from (https://doi.org/10.6084/m9.figshare.9204998).
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Acknowledgements
The data and samples used for this research were obtained from UK biobank. Data on cardiac function assessed by MRI is contributed by Pirruccello and his colleagues. Data on frailty index is contributed by Atkins and his colleagues. We would like to thank Pirruccello and his colleagues, Atkins and his colleagues, and UK Biobank participants and coordinators for their contribution to this dataset.
Funding
This work was supported by National Key Research and Development Programme of China (2018YFC2000400, 2018YFC2000400-3, 2018YFC2002000) and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01).
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HZ, MH and XW designed the research; HZ, MH, YL, XH, ZH and XJ conducted the research; HZ, MH, ZH and YL analysed the data and performed the tactical analyses. HZ and XW wrote the paper; ZL and XW supervised the study, and all authors read and approved the final manuscript.
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Zhang, H., Hao, M., Hu, Z. et al. Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index: A Mendelian Randomization Study. Phenomics 2, 430–437 (2022). https://doi.org/10.1007/s43657-022-00072-z
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DOI: https://doi.org/10.1007/s43657-022-00072-z