The influence of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study

INTRODUCTION

Risk factors for chronic back pain (CBP) include not only intervertebral disc degeneration but also psychological make-up and social influences (1). Our previous work suggested that such risk factors share genetic influence with CBP (2). Shared underlying genetic influence makes risk factors difficult to study using conventional epidemiological methods. New methods which use genetic factors as instruments or surrogate measures can overcome these difficulties to some extent. Using large, publicly available datasets we conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of educational years, smoking, alcohol consumption, physical activity, sleep and depression on CBP and the causal effect of CBP on these 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. To strengthen the confidence in our findings we used a combination of methods. 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 if 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 years of schooling (OR per 4.2 years = 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 the 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

Our work revealed that fewer years of schooling, smoking, greater alcohol consumption and major depressive disorder all increase the risk of CBP. Examination of the reverse direction showed that, unsurprisingly, CBP increases the risk of greater alcohol consumption and smoking. Our findings are robust to confounding because genetic instruments reduce this epidemiological limitation. This work suggests that public health measures childhood and early adulthood and the recognition and prompt treatment of depression may reduce the population burden of CBP. Randomised controlled clinical trials based on population samples should be explored.

REFERENCES

1. A. J. MacGregor, T. Andrew, P. N. Sambrook and T. D. Spector Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. Arthritis Rheum 2004 Vol. 51 Issue 2 Pages 160-7
2. M. B. Freidin et al., "Insight into the genetic architecture of back pain and its risk factors from a study of 509,000 individuals," Pain, vol. 160, no. 6, pp. 1361-1373