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Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study

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Abstract

Purpose

Risk factors for chronic back pain (CBP) may share underlying genetic factors, making them difficult to study using conventional methods. We conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of risk factors (education, smoking, alcohol consumption, physical activity, sleep and depression) on CBP and the causal effect of CBP on the same risk factors.

Methods

Genetic instruments for risk factors and CBP were obtained from the largest published genome-wide association studies (GWAS) of risk factor traits conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis (IVW), Causal Analysis Using Summary Effect (CAUSE) and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results with IVW or CAUSE were statistically significant after accounting for multiple statistical testing (p < 0.003), and the direction and magnitude of effect estimates were concordant between IVW, CAUSE, and sensitivity analyses.

Results

We found evidence for statistically significant causal associations between greater education (OR per 4.2 years of schooling = 0.54), ever smoking (OR = 1.27), greater alcohol consumption (OR = 1.29 per consumption category increase) and major depressive disorder (OR = 1.41) and risk of CBP. Conversely, we found evidence for significant causal associations between CBP and greater alcohol consumption (OR = 1.19) and between CBP and smoking (OR = 1.21). Other relationships did not meet our pre-defined criteria for causal association.

Conclusion

Fewer years of schooling, smoking, greater alcohol consumption, and major depressive disorder increase the risk of CBP. CBP increases the risk of greater alcohol consumption and smoking.

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Acknowledgements

Dr. Tsepilov was supported by the Russian Foundation for Basic Research (#20-04-00464). Dr. Aulchenko was supported by the Russian Ministry of Education and Science under the 5-100 Excellence Programme, 0259-2021-0009/АААА-А17-117092070032-4. Ms. Elgaeva was supported by the budget project #FWNR-2022-0020. Dr. Suri is an employee of the VA Puget Sound Health Care System and affiliated with the University of Washington Clinical Learning, Evidence and Research (CLEAR) Center, which was funded by NIAMS/NIH P30AR072572. The contents of this work do not represent the views of the US Department of Veterans Affairs, the National Institutes of Health, or the US Government. The study was conducted using the UK Biobank Resource under project #18219. We are grateful to the UK Biobank participants for making such research possible. We thank Dr. Alexandra Shadrina for the help with the development of the MR protocol.

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Author notes

  1. Frances M. K. Williams and Elizaveta E. Elgaeva have contributed equally to this work. Yakov A. Tsepilov and Pradeep Suri have contributed equally to this work.

Authors and Affiliations

  1. Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College London, London, UK

    Frances M. K. Williams & Maxim B. Freidin

  2. Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia

    Elizaveta E. Elgaeva, Yurii S. Aulchenko & Yakov A. Tsepilov

  3. Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk, Russia

    Elizaveta E. Elgaeva & Yakov A. Tsepilov

  4. Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia

    Olga O. Zaytseva

  5. PolyOmica, ‘s-Hertogenbosch, The Netherlands

    Yurii S. Aulchenko

  6. Kurchatov Genomics Center, Institute of Cytology & Genetics, Novosibirsk, Russia

    Yurii S. Aulchenko

  7. Division of Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, USA

    Pradeep Suri

  8. Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, S-152-ERIC, 1660 S. Columbian Way, Seattle, WA, 98108, USA

    Pradeep Suri

  9. Department of Rehabilitation Medicine, University of Washington, Seattle, USA

    Pradeep Suri

  10. Clinical Learning, Evidence, and Research (CLEAR) Center, University of Washington, Seattle, USA

    Pradeep Suri

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  1. Frances M. K. Williams
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Correspondence to Pradeep Suri.

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Conflict of interest

YSA is a cofounder and a co-owner of PolyOmica and PolyKnomics, private organizations providing services, research, and development in the field of computational and statistical genomics. OOZ is an employee of Genos Glycoscience Research Laboratory. The other authors declare that they have no competing interests.

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Williams, F.M.K., Elgaeva, E.E., Freidin, M.B. et al. Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study. Eur Spine J 31, 1906–1915 (2022). https://doi.org/10.1007/s00586-022-07263-2

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