Causal association of sleep disturbances and low back pain: A bidirectional two-sample Mendelian randomization study

Ge Luo; Yuanyuan Yao; Jiachun Tao; Tingting Wang; Min Yan

doi:10.3389/fnins.2022.1074605

Causal association of sleep disturbances and low back pain: A bidirectional two-sample Mendelian randomization study

Front Neurosci. 2022 Dec 2:16:1074605. doi: 10.3389/fnins.2022.1074605. eCollection 2022.

Authors

Ge Luo¹, Yuanyuan Yao¹, Jiachun Tao¹, Tingting Wang¹, Min Yan¹

Affiliation

¹ Department of Anesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Background: Previous observational studies have shown that low back pain (LBP) often coexists with sleep disturbances, however, the causal relationship remains unclear. In the present study, the causal relationship between sleep disturbances and LBP was investigated and the importance of sleep improvement in the comprehensive management of LBP was emphasized.

Methods: Genetic variants were extracted as instrumental variables (IVs) from the genome-wide association study (GWAS) of insomnia, sleep duration, short sleep duration, long sleep duration, and daytime sleepiness. Information regarding genetic variants in LBP was selected from a GWAS dataset and included 13,178 cases and 164,682 controls. MR-Egger, weighted median, inverse-variance weighted (IVW), penalized weighted median, and maximum likelihood (ML) were applied to assess the causal effects. Cochran's Q test and MR-Egger intercept were performed to estimate the heterogeneity and horizontal pleiotropy, respectively. Outliers were identified and eliminated based on MR-PRESSO analysis to reduce the effect of horizontal pleiotropy on the results. Removing each genetic variant using the leave-one-out analysis can help evaluate the stability of results. Finally, the reverse causal inference involving five sleep traits was implemented.

Results: A causal relationship was observed between insomnia-LBP (OR = 1.954, 95% CI: 1.119-3.411), LBP-daytime sleepiness (OR = 1.011, 95% CI: 1.004-1.017), and LBP-insomnia (OR = 1.015, 95% CI: 1.004-1.026), however, the results of bidirectional MR analysis between other sleep traits and LBP were negative. The results of most heterogeneity tests were stable and specific evidence was not found to support the disturbance of horizontal multiplicity. Only one outlier was identified based on MR-PRESSO analysis.

Conclusion: The main results of our research showed a potential bidirectional causal association of genetically predicted insomnia with LBP. Sleep improvement may be important in comprehensive management of LBP.

Keywords: Mendelian randomization; causal effect; insomnia; low back pain; sleep disturbance.