Abstract
Background Ageing traits and frailty are important health issues in modern medicine. Evidence supporting the causal effects from tobacco smoking on various ageing traits is warranted.
Methods This Mendelian randomization (MR) analysis instrumented 377 genetic variants associated with being an ever smoker in a genome-wide significant level to test the causal estimates from tobacco smoking. The outcome data included 337,318 white British ancestry UK Biobank participants. Leukocyte telomere length, appendicular lean mass index, subjective walking pace, handgrip strength, and wristband accelerometry determined physical activity degree were collected as ageing related outcomes. Summary-level MR by inverse variance weighted method and pleiotropy-robust MR methods, including weighted median and MR–Egger, was performed.
Results Summary-level MR analysis indicated that higher genetic predisposition for tobacco smoking was significantly associated with shorter leukocyte telomere length [2-fold prevalence increase in smoking towards standardized Z-score, -0.041 (-0.054, -0.028)], lower appendicular lean mass index [-0.007 (-0.010, -0.005)], slower walking pace [ordinal category, -0.047 (-0.054, -0.033)], and lower time spent on moderate-to-vigorous physical activity [hours per week, -0.39 (-0.56, -0.23). The causal estimates were nonsignificant towards handgrip strength phenotype [kg, 0.074 (-0.055, 0.204)]. Pleiotropy-robust MR results generally supported the main causal estimates.
Conclusion Genetically predicted tobacco smoking is significantly associated with worse ageing phenotypes. Healthcare providers may continue to reduce tobacco use which may be helpful to reduce the burden related to ageing and frailty.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This research was supported by a grant of the MD-Phd/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT, Ministry of Science and ICT) (No. 2021R1A2C2094586). The study was performed independently by the authors.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The study was approved by the institutional review boards of Seoul National University Hospital (No. E-2203-053-1303) and the UK Biobank consortium (application No. 53799).11,15 The study was performed in accordance with the Declaration of Helsinki. The requirement for informed consent was waived by the attending institutional review boards because this study investigated public anonymous database without medical intervention.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
The data used for this study is available in the public database. The CKDGen data is openly available in the consortium website (URL: https://ckdgen.imbi.uni-freiburg.de/) and the UK Biobank data is accessible after acquiring approval from the organization (application No. 53799).