Association of Oxidative Stress on Cognitive Function: A Bidirectional Mendelian Randomisation Study

Area of Science:

• Genetics
• Neuroscience
• Biochemistry

Background:

• Oxidative stress is implicated in various health conditions, including cognitive decline.
• Antioxidant enzymes play a crucial role in mitigating oxidative stress.
• Understanding the genetic links between antioxidant enzymes and cognitive function is essential for public health.

Purpose of the Study:

• To investigate the potential causal relationship between key antioxidant enzymes and various aspects of cognitive function.
• To explore the association between genetic variants of antioxidant enzymes and cognitive performance, intelligence, memory, and reaction time.
• To examine bidirectional causal links using Mendelian randomization.

Main Methods:

• Utilized a bidirectional Mendelian randomization study design.
• Identified independent genetic variants associated with glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin (PRDX), sulfhydryl oxidase (SOX), and thyroid peroxidase (TPO) via genome-wide association studies (GWAS).
• Employed the inverse variance weighted (IVW) or Wald ratio method to analyze the associations.

Main Results:

• Significant positive associations were found between genetically predicted GST and TPO and enhanced cognitive performance.
• GST and TPO were also significantly associated with higher intelligence.
• Additional associations included SOX with cognitive performance, TPO with memory recall (digit span), and SOX with reaction time.
• No significant associations were observed for speech, linguistic disorders, or visual disturbances.
• No evidence of reverse causation was detected.

Conclusions:

• The study provides evidence supporting a potential causal role of oxidative stress, specifically through enzymes like GST and TPO, in influencing cognitive function and intelligence.
• Findings highlight the importance of antioxidant defense mechanisms in maintaining cognitive health.
• Further research is warranted to explore therapeutic strategies targeting oxidative stress for cognitive enhancement.