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Epidemiology and Population Health

Causal effects from tobacco smoking initiation on obesity-related traits: a Mendelian randomization study

International Journal of Obesity volume 47, pages 1232–1238 (2023)Cite this article

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Abstract

Background

There is a widespread notion that tobacco smoking controls weight based on the appetite suppressive effect of nicotine. However, the causal relationship between smoking initiation and obesity-related traits in the general population are unclear.

Methods

This Mendelian randomization analysis utilized 378 genetic variants associated with tobacco smoking initiation (usually in adolescence or young adulthood) identified in a genome-wide association study (meta-analysis) of 1.2 million individuals. Outcome data for body mass index, waist circumference, hip circumference, and waist-to-hip ratio were extracted from the 337,138 white British-ancestry UK Biobank participants aged 40–69 years. Replication analyses were performed for genome-wide association study meta-analysis for body mass index, including the GERA/GIANT data including 364,487 samples from mostly European individuals. In addition, summary-level Mendelian randomization by inverse variance weighted method and pleiotropy-robust Mendelian randomization methods, including median-based and MR–Egger regression, was performed.

Results

Summary-level Mendelian randomization analysis indicated that genetically predicted smoking initiation is causally linked to higher body mass index [+0.28 (0.18–0.38) kg/m2], waist circumference [+0.88 (0.66–1.10) cm], hip circumference [+0.40 (0.23–0.57) cm], and waist-to-hip ratio [+0.006 (0.005–0.007)]. These results were consistent with those of the pleiotropy-robust Mendelian randomization analysis. Additionally, in replication analysis, genetically predicted smoking initiation was significantly associated with a higher body mass index [+0.03 (0.01, 0.05] kg/m2).

Conclusion

Tobacco initiation may lead to worse obesity-related traits in the general 40- to 69-year-old individuals. Therefore, tobacco-use initiation as a long-term weight-control measure should be discouraged.

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Fig. 1: Study flow diagram.
Fig. 2: Causal estimates from the Mendelian randomization analysis.

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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). The summary statistics for the GERA/GIANT meta-analysis is available in the GWAS catalog (https://www.ebi.ac.uk/gwas/studies/GCST006368). Dr. Dong Ki Kim and Dr. Sehoon Park had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The data for this study are available in the public domain, as described in the manuscript.

Code availability

The codes used for the statistical analyses in this study are available from each statistical package and the name of the packages are provided in the methods section.

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Acknowledgements

The study was based on the data provided by the UK Biobank consortium (application No. 53799). We thank the investigators of the CKDGen, GERA, and GIANT consortium who provided the summary statistics for the outcome data of this study.

Funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI23C1484). 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). This research was supported by the research fund from Seoul National University (3020210020). The funder played no role in the performance of the study, and the study was performed independently by the authors.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

    Sehoon Park & Yon Su Kim

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

    Sehoon Park, Seong Geun Kim, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Kwon Wook Joo, Yon Su Kim & Dong Ki Kim

  3. Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Seoul, Korea

    Soojin Lee

  4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

    Soojin Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim & Dong Ki Kim

  5. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea

    Yaerim Kim

  6. Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Gyeonggi-do, Korea

    Semin Cho

  7. Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea

    Kwangsoo Kim

  8. Kidney Research Institute, Seoul National University, Seoul, Korea

    Seung Seok Han, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim & Dong Ki Kim

  9. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea

    Jung Pyo Lee & Chun Soo Lim

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  1. Sehoon Park
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Contributions

The corresponding author attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted. SP, HL, KSK, KWJ, and DKK contributed to the conception and design of the study. SL, SK, YK, YCK, SSH, JPL, KWJ, CSL, YSK, and DKK provided statistical advice and interpreted the data. SP and KSK performed the main statistical analysis, assisted by SK, SL, and YK. HL, JPL, KWJ, CSL, YSK, and DKK provided advice regarding the data interpretation. YCK, SSH, HL, JPL, KWJ, CSL, and YSK provided material support during the study. SP and DKK had full access to all data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. All authors participated in drafting the manuscript. All authors reviewed the manuscript and approved the final version to be published.

Corresponding author

Correspondence to Dong Ki Kim.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This 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) [14, 15], and was performed in accordance with the Declaration of Helsinki. The requirement for informed consent was waived by the attending institutional review boards because anonymous public databases were used for collecting data for research purposes.

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Park, S., Kim, S.G., Lee, S. et al. Causal effects from tobacco smoking initiation on obesity-related traits: a Mendelian randomization study. Int J Obes 47, 1232–1238 (2023). https://doi.org/10.1038/s41366-023-01371-9

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