Introduction

Persistent back pain (BP) is a common debilitating condition leading the list of disorders causing disability in much of the world. It leads to work absenteeism, job loss and long-term disability. In Europe, the costs of BP are estimated to amount to 1%-2% of GDP. Predicting the development of persistent BP may contribute to reducing its burden on society and healthcare by offering stratified clinical management early in the condition. The use of polygenic risk scores (PRS) is a promising approach to stratifying individuals into risk groups based on their genetic make-up across the whole genome. BP is heritable (30%-60%), therefore the use of PRS for this disorder may be fruitful as has been demonstrated in other common complex traits. In the current study we explored the utility of PRS for BP using UK Biobank and TwinsUK data.

Methods

We used summary statistics from our published UK Biobank genome-wide association study for BP in North Europeans (n = 450,000) to calculate a weighted PRS across multiple p-value thresholds. The PRS were tested for association with disabling and non-disabling BP in TwinsUK data (n = 1,812 and 4,135, respectively). We used the coefficient of determination (R²) to select PRS with the highest predictive capacity and then calculated prevalence of BP phenotypes in various percentiles of the PRS. Based on the results we selected percentile thresholds to stratify individuals into high, medium and low risk groups followed by a comparison of prevalence of BP in high and low risk groups versus medium risk.

Results

The PRS with the highest R² (R² = 0.01) comprised 7,269 genetic variants with p-value < 1e-3 for association with BP in UK Biobank. We established that individuals with PRS below 20% and above 80% of the PRS distribution exhibit lower and higher prevalence of BP, respectively, compared to mean in TwinsUK. For both disabling and non-disabling BP there were statistically significant lower or higher odds of BP in respective percentile groups compared to medium risk group (Table).

Discussion

To the best of our knowledge, this is the first report considering PRS as a potential tool to predict the risk of BP. The results of the study suggest predictive capacity of PRS and warrant further research using a combination of PRS and available clinical tools, such as the STarT Back clinical tool which helps to match primary care patients to the most suitable treatment.

Acknowledgement

The use of UK Biobank data was approved under the project #18219.