A Two-Sample Mendelian Randomization Research Examining the Causal Association Between Ischemic Stroke and...

Area of Science:

• Neurology
• Genetics
• Sleep Medicine

Background:

• Observational studies suggest a link between ischemic stroke (IS) and obstructive sleep apnea (OSA).
• The precise causal relationship between IS subtypes and OSA remains unclear.
• Mendelian randomization (MR) can investigate potential causal links using genetic variants.

Purpose of the Study:

• To evaluate the causal association between IS subtypes (large artery stroke [LAS], cardioembolic stroke [CES], small vessel stroke [SVS]) and OSA.
• To utilize a Mendelian randomization approach to assess these relationships.
• To clarify the etiological connection between stroke and sleep apnea.

Main Methods:

• Two-sample Mendelian randomization analysis was performed using European population data.
• Investigated IS (n=440,328), LAS (n=410,484), CES (n=413,304), SVS (n=198,048), and OSA (n=451,618).
• Inverse variance-weighted (IVW) method was primary; sensitivity analyses included leave-one-out, MR-Egger, and MR-PRESSO tests.

Main Results:

• Gene-predicted CES showed a significant association with increased OSA risk (IVW: OR=1.07, p=0.004).
• No direct causal association was found between IS, LAS, or SVS and OSA incidence.
• Sensitivity analyses confirmed no significant heterogeneity or bias.

Conclusions:

• Cardioembolic stroke (CES) is identified as a risk factor for obstructive sleep apnea (OSA).
• No direct causal link exists between other IS subtypes (LAS, SVS) and OSA.
• A positive genetic correlation between CES and OSA is indicated.