No genetic causal relationship between lung function and osteoporosis ― evidence from a mendelian randomization study

Abstract

Abstract For a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level. To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran’s Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy. In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the. results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors.

Keywords

• Lung function
• Osteoporosis
• Bone mineral density
• Mendelian randomization