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

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/m 2 ) 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 These slides can be retrieved under Electronic Supplementary Material.