ISSLS Prize in Clinical Science 2020. Examining causal effects of body mass index on back pain: a Mendelian randomization study

Abstract

Purpose

Measures of body fat accumulation are associated with back pain, but a causal association is unclear. We hypothesized that BMI would have causal effects on back pain. We conducted a two-sample Mendelian randomization (MR) study to assess the causal effect of body mass index (BMI) on the outcomes of (1) back pain and (2) chronic back pain (duration > 3 months).

Methods

We identified genetic instrumental variables for BMI (n = 60 variants) from a meta-analysis of genome-wide association studies (GWAS) conducted by the Genetic Investigation of ANthropometric Traits consortium in individuals of European ancestry (n = 322,154). We conducted GWAS of back pain and chronic back pain (n = 453,860) in a non-overlapping sample of individuals of European ancestry. We used inverse-variance weighted (IVW) meta-analysis as the primary method to estimate causal effects.

Results

The IVW analysis showed evidence supporting a causal association of BMI on back pain, with a 1-standard deviation (4.65 kg/m2) increase in BMI conferring 1.15 times the odds of back pain (95% confidence interval [CI]: 1.06–1.25, p = 0.001]; effects were directionally consistent in secondary analysis and sensitivity analyses. The IVW analysis supported a causal association of BMI on chronic back pain (OR 1.20 per 1 SD deviation increase in BMI [95% CI 1.09–1.32; p = 0.0002]), and effects were directionally consistent in secondary analysis and sensitivity analyses.

Conclusion

In this first MR study of BMI and back pain, we found a significant causal effect of BMI on both back pain and chronic back pain.

Graphic abstract

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Acknowledgements

Dr. Suri’s participation in this study was funded by VA Puget Sound Health Care System and by a VA Career Development Award 1IK2RX001515. The contents of this work do not represent the views of the US Department of Veterans Affairs or the US Government. Dr. Aulchenko was supported by the Russian Ministry of Education and Science under the 5-100 Excellence Programme and by the Federal Agency of Scientific Organizations via the Institute of Cytology and Genetics (project 0324-2019-0040). Ms. Elgaeva and Dr. Tsepilov were supported by the Russian Foundation for Basic Research (project 19-015-00151). 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.

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Correspondence to Pradeep Suri.

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Elgaeva, E.E., Tsepilov, Y., Freidin, M.B. et al. ISSLS Prize in Clinical Science 2020. Examining causal effects of body mass index on back pain: a Mendelian randomization study. Eur Spine J 29, 686–691 (2020). https://doi.org/10.1007/s00586-019-06224-6

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Keywords

  • Low back pain
  • Epidemiology
  • Prognosis
  • Risk factor
  • Obesity