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Original research
Associations between modifiable risk factors and frailty: a Mendelian randomisation study
  1. Nan Zhang1,
  2. Ziheng Jia1,
  3. Tianshu Gu1,
  4. Yi Zheng1,
  5. Yunpeng Zhang1,
  6. Wenhua Song1,
  7. Ziliang Chen1,
  8. Guangping Li1,
  9. Gary Tse1,2,3,
  10. Tong Liu1
  1. 1 Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
  2. 2 Kent and Medway Medical School, University of Kent and Canterbury Christ Church University, Canterbury, Kent, UK
  3. 3 School of Nursing and Health Studies, Hong Kong, Metropolitan University, Hong Kong, China
  1. Correspondence to Professor Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Hexi District, Tianjin 300211, China; liutongdoc{at}126.com; Professor Gary Tse, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Hexi District, Tianjin 300211, People's Republic of China; gary.tse{at}kmms.ac.uk

Abstract

Background Early identification of modifiable risk factors is essential for the prevention of frailty. This study aimed to explore the causal relationships between a spectrum of genetically predicted risk factors and frailty.

Methods Univariable and multivariable Mendelian randomisation (MR) analyses were performed to explore the relationships between 22 potential risk factors and frailty, using summary genome-wide association statistics. Frailty was accessed by the frailty index.

Results Genetic liability to coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), ischaemic stroke, atrial fibrillation and regular smoking history, as well as genetically predicted 1-SD increase in body mass index, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, alcohol intake frequency and sleeplessness were significantly associated with increased risk of frailty (all p<0.001). In addition, there was a significant inverse association between genetically predicted college or university degree with risk of frailty (beta −0.474; 95% CI (−0.561 to –0.388); p<0.001), and a suggestive inverse association between high-density lipoprotein cholesterol level with risk of frailty (beta −0.032; 95% CI (−0.055 to –0.010); p=0.004). However, no significant causal associations were observed between coffee consumption, tea consumption, serum level of total testosterone, oestradiol, 25-hydroxyvitamin D, C reactive protein or moderate to vigorous physical activity level with frailty (all p>0.05). Results of the reverse directional MR suggested bidirectional causal associations between T2DM and CAD with frailty.

Conclusions This study provided genetic evidence for the causal associations between several modifiable risk factors with lifetime frailty risk. A multidimensional approach targeting these factors may hold a promising prospect for prevention frailty.

  • prevention
  • aging
  • cardiovascular diseases
  • epidemiology
  • genetics

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

https://doi.org/10.1136/jech-2023-220882

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information.

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    Footnotes

    • GT and TL are joint senior authors.

    • Contributors All authors have read and approved of the submission of this manuscript. NZ and TL contributed to the study concept and design. NZ, ZJ and TG contributed to the acquisition, analysis and interpretation of data. NZ, YZheng, YZhang, WS, ZC, GL and GT drafted the manuscript. TL is the guarantor. All authors contributed to critical revisions of the manuscript for important intellectual content.

    • Funding This work was funded by the National Natural Science Foundation of China (81970270, 82170327 to TL), Tianjin Natural Science Foundation (20JCZDJC00340, 20JCZXJC00130 to TL) and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-029A).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.