C-reactive protein and cognitive impairment: A bidirectional Mendelian randomization study

Area of Science:

• Neuroscience
• Genetics
• Inflammation Research

Background:

• C-reactive protein (CRP) is a known risk factor for cognitive impairment.
• Observational studies suggest a link, but causal relationships remain unclear.
• Mendelian randomization (MR) can investigate genetic associations to infer causality.

Purpose of the Study:

• To determine the causal association between C-reactive protein (CRP) and cognitive impairment using bidirectional Mendelian randomization (MR).
• To investigate the genetic link between CRP levels and various cognitive functions.

Main Methods:

• Utilized genome-wide association studies (GWAS) summary statistics for CRP and cognitive traits (performance, fluid intelligence, prospective memory, reaction time).
• Employed bidirectional MR analysis with multiple methods (IVW, MR Egger, weighted median, etc.).
• Conducted MR sensitivity analyses to assess pleiotropy and heterogeneity.

Main Results:

• Forward MR indicated a significant association between genetically proxied CRP and prospective memory (P=0.009).
• Little evidence supported CRP's association with other cognitive tests.
• Reverse MR suggested potential associations between genetically proxied cognitive performance/fluid intelligence and CRP levels (P=0.002, P=0.019).

Conclusions:

• Genetically proxied CRP impacts prospective memory, but not other cognitive measures.
• Evidence suggests a bidirectional relationship, with cognition potentially influencing CRP levels.
• MR sensitivity analyses confirmed the robustness of the CRP-prospective memory association.