Causal Relationship of Obstructive Sleep Apnea with Bone Mineral Density and the Role of BMI

Abstract

Background

Observational studies have yielded conflicting evidence concerning the relationships between obstructive sleep apnea (OSA) and bone mineral density (BMD). As the exact causal inferences remain inconclusive, we conducted a two-sample Mendelian randomization (MR) to identify the causal associations between OSA and BMD.

Methods

Single-nucleotide polymorphisms associated with OSA were extracted from the FinnGen study. Summary statistics for 10 BMD measured at different age or skeletal sites were obtained from the publicly available IEU GWAS database. Inverse-variance weighted (IVW) method was chosen as the primary analysis, combined with several sensitivity analyses to evaluate the robustness of results. The study design included two-sample MR and network MR.

Results

Our primary MR analysis revealed that genetically predicted OSA was positively linked to increased forearm BMD (β = 0.24, 95% confidence interval [CI]: 0.06–0.41, p = 0.009) and heel BMD (β=0.10, 95% CI = 0.02–0.18, p = 0.018), while no significant causal relationships were observed between OSA and total body BMD, lumbar spine BMD, or femoral neck BMD (all p > 0.05). Network MR suggests that OSA might act as a mediating factor in the effect of BMI on forearm BMD and heel BMD, with a mediated portion estimated at 73% and 84%, respectively.

Conclusion

Our findings provide support for a causal relationship between genetically predicted OSA and increased forearm BMD and heel BMD. Furthermore, our results suggest that OSA may play a role in mediating the influence of BMI on BMD.

Keywords:

• obstructive sleep apnea
• bone mineral density
• BMI
• Mendelian randomization

Data Sharing Statement

All data are publicly available GWAS summary data. This data can be found at open GWAS (https://gwas.mrcieu.ac.uk/) and GEFOS Consortium (http://www.gefos.org/).

Ethics Declaration

All genome-wide association studies included in this study had been approved by a relevant review board, and participants had provided written informed consent. The study had also been approved by Zhongshan Boai hospital’s ethics committee.

Acknowledgments

The authors are grateful to the authors of the original studies for sharing the genome-wide association studies (GWASs) summary statistics in the present study.

Disclosure

The authors declared no conflict of interest.