Genetic Liability to Bone Mineral Density and Functional Outcome After Ischemic Stroke

An increasing amount of research indicates that bone mineral density (BMD) could impact the functional outcome after ischemic stroke (FOAIS). However, the specific connection between BMD and FOAIS is still not clear. Hence, we utilized the Mendelian randomization method to examine the genetic predisposition to BMD in connection with FOAIS.

Instrumental variables for BMD, heel bone mineral density T score (HBMDTS), and lumbar spine bone mineral density (LSBMD) were identified from genome-wide association study data of individuals with European ancestry. The study on FOAIS data came from European ancestry patients and was carried out by the Genetics of Ischemic Stroke (IS) Functional Outcome network. The inverse variance weighted method was employed to assess the genetic correlation between BMD and FOAIS. To assess the reliability of the results, sensitivity analyses were performed employing alternative Mendelian randomization techniques, such as the weighted median approach and MR analysis using the Robust Adjusted Profile Score. Furthermore, the intercept from MR-Egger regression was applied to identify possible pleiotropic effects. The variability among genetic variants was evaluated through I² and Q statistics.

Genetic liability to HBMDTS was associated with poor FOAIS at 3 months (mRS 3-6, IVW OR = 1.30; 95% CI = 1.09-1.54; p = 0.003, p-Bonferroni = 0.009). Even after adjusting for relevant factors, significant associations remained (mRS 3-6, IVW OR = 1.33; 95% CI = 1.09-1.63; p = 0.006, p-Bonferroni = 0.017). No significant causal effects were observed for total BMD or LSBMD on FOAIS. Sensitivity analyses showed no evidence of pleiotropy or heterogeneity.

Genetic predisposition to HBMDTS was associated with poor FOAIS. This research provides a genetic basis for the association between HBMDTS and poor FOAIS, potentially impacting the clinical significance of recovery for stroke patients.