Disentangling the relationship between fibromyalgia and insomnia: A bidirectional two-sample Mendelian random analysis

Fibromyalgia (FM) and insomnia frequently coexist, but whether FM is an independent causal risk factor for insomnia, and/or vice versa, remains unclear. We investigated the bidirectional causal relationship between FM and insomnia.

Methods

Genome-wide association studies (GWAS) summary statistics on FM [sample size = 416,757 (2689 cases; 299,606 controls) (FinnGen)] and insomnia [sample size = 462,341 (UK Biobank)] were used. The possible causal relationships were assessed by bi-directional MR analysis. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger, weighted median, weighted mode and simple mode approaches. In addition, sensitivity analyses including Cochran’s Q test, MR-Egger intercept test, and the leave-one-out test were conducted to ensure the stability of the results.

Results

There was strong evidence to suggest insomnia is a risk factor for FM (odds ratio (OR) 7.65, 95% confidence interval (CI) 3.17-18.45, p = 5.85E-06). We found no evidence that genetic liability to FM increases insomnia (OR = 1.00, 95% CI 0.99-1.01, p = 0.99)

Conclusions

This study provides evidence in support of a causal relationship between insomnia and increased risk of FM, whilst overcoming the major limitations of previous epidemiological studies. Interventions for insomnia may be an effective strategy to prevent or reduce the burden of FM. Extended study needs to be performed with multi-center, large-scale GWAS cohort studies to re-evaluate the association between FM and insomnia in future.