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Causal effects of blood pressure and the risk of frailty: a bi-directional two-sample Mendelian randomization study

Journal of Human Hypertension volume 38, pages 329–335 (2024)Cite this article

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Abstract

Observational studies have indicated that high blood pressure (BP) may be a risk factor to frailty. However, the causal association between BP and frailty remains not well determined. The purpose of this bi-directional two-sample Mendelian randomization (MR) study was to investigate the causal relationship between BP and frailty. Independent single nucleotide polymorphisms (SNPs) strongly (P < 5E-08) associated with systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) were selected as instrumental variables. Two different published genome-wide association studies (GWAS) on BP from the CHARGE (n = 810,865) and ICBP (n = 757,601) consortia were included. Summary-level data on frailty index (FI) were obtained from the latest GWAS based on UK Biobank and Swedish TwinGene cohorts (n = 175,226). Inverse variance weighted (IVW) approach with other sensitivity analyses were used to calculate the causal estimate. Using the CHARGE dataset, genetic predisposition to increased SBP (β = 0.135, 95% CI = 0.093 to 0.176, P = 1.73E-10), DBP (β = 0.145, 95% CI = 0.104 to 0.186, P = 3.14E-12), and PP (β = 0.114, 95% CI = 0.070 to 0.157, p = 2.87E-07) contributed to a higher FI, which was validated in the ICBP dataset. There was no significant causal effect of FI on SBP, DBP, and PP. Similar results were obtained from different MR methods, indicating good stability. There was potential heterogeneity detected by Cochran’s Q test, but no horizontal pleiotropy was observed in MR-Egger intercept test (P > 0.05). These findings evinced that higher BP and PP were causally associated with an increased risk of frailty, suggesting that controlling hypertension could reduce the risk of frailty.

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Fig. 1: Study design and three assumptions of this bi-directional two-sample Mendelian randomization study.
Fig. 2: Causal association of SBP, DBP, and PP on frailty index.
Fig. 3: Scatter plots for the causal effects of SBP, DBP, and PP on frailty index.

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Data availability

The GWAS summary statistics data used in this MR study are all publicly available in GWAS Catalog (https://www.ebi.ac.uk/gwas/home).

Code availability

This paper does not report the original code.

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Acknowledgements

The authors acknowledge all the participants, researchers, and consortia who contributed to this study.

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Author notes

  1. These authors contributed equally: Ge Tian, Rong Zhou.

Authors and Affiliations

  1. Xi’an Medical University, Xi’an, 710021, Shaanxi, China

    Ge Tian & Rui Li

  2. Department of Geriatric Neurology, Shaanxi Provincial People’s Hospital, Xi’an, 710068, Shaanxi, China

    Ge Tian, Rong Zhou, Xingzhi Guo & Rui Li

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Contributions

GT, XG, and RL conceived and designed the study. GT, RZ, and XG collected and analyzed the data. GT and RZ drafted the manuscript. XG and RL revised the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Xingzhi Guo or Rui Li.

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This study was performed based on publicly available data and no separate ethical approval and consent was required.

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Tian, G., Zhou, R., Guo, X. et al. Causal effects of blood pressure and the risk of frailty: a bi-directional two-sample Mendelian randomization study. J Hum Hypertens 38, 329–335 (2024). https://doi.org/10.1038/s41371-024-00901-w

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