Genetic causality between insomnia and specific orthopedic conditions: Insights from a two-sample Mendelian randomization study

Objective

To investigate the genetic causality for the insomnia and common orthopedic diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoporosis (OP), and gout (GT).

Methods

The genome-wide association study (GWAS) summary data on insomnia were obtained from a published study, while the GWAS summary data on RA, AS, OP, and GT were sourced from the FinnGen consortium. We utilized the TwoSampleMR package of the R software (version 4.1.2) to conduct a two-sample Mendelian randomization (MR) analysis. Our primary method of analysis was the random-effects inverse variance weighted (IVW) approach. Subsequently, we conducted a series of sensitivity analyses for the MR analysis.

Results

The MR analysis revealed a positive genetic causal relationship between insomnia and RA (P = 0.016, odds ratio [OR] 95 % confidence interval [CI] = 1.112 [1.020–1.212]). However, no significant genetic causal relationship was observed between insomnia and AS (P = 0.194, OR 95 % CI = 1.121 [0.944–1.331]), OP (P = 0.788, OR 95 % CI = 1.016 [0.904–1.142]), and GT (P = 0.757, OR 95 % CI = 1.018 [0.912–1.136]). The MR analysis did not exhibit heterogeneity, horizontal pleiotropy, outlier effects, or dependence on a single SNP, and demonstrated normal distribution, which guaranteed the robustness of the results.

Conclusion

The results of this study suggest that insomnia may be a significant risk factor for RA, and controlling insomnia may represent a promising strategy for preventing RA. While insomnia was not observed to be associated with AS, OP, and GT at the genetic level, other levels of association cannot be excluded.