Assessing the bidirectional causal relationship between malnutrition, self-reported fatigue, and stroke: A 2-sample...

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Understanding the causal factors of stroke is crucial for public health.
• The relationship between fatigue, malnutrition, and stroke risk requires further investigation.

Purpose of the Study:

• To investigate the bidirectional causal relationships between malnutrition, fatigue, and stroke using Mendelian randomization.
• To identify if fatigue or malnutrition are risk factors for stroke or its subtypes.

Main Methods:

• Utilized a 2-sample Mendelian randomization (MR) analysis with publicly available Genome-Wide Association Study summary statistics.
• Employed inverse-variance weighted (IVW) and weighted median methods for primary analysis.
• Conducted sensitivity analyses (Cochran Q, MR Egger intercept, MR-PRESSO) to assess heterogeneity and pleiotropy.

Main Results:

• Self-reported fatigue showed a significant causal association with any stroke (OR 1.43, P=0.028).
• No significant causal relationships were found between fatigue and stroke subtypes, or between malnutrition and any stroke.
• No significant bidirectional causal effects were detected between stroke and fatigue or malnutrition.

Conclusions:

• Fatigue is identified as a potential risk factor for overall stroke incidence.
• Biological pathways potentially mediating the link between fatigue and stroke involve CREB transcription factor activity, synaptic function, and plasma membrane processes.
• Malnutrition does not appear to have a causal relationship with stroke risk.