Association between brain connectivity and renal pathophysiology: a multi-trait Mendelian randomization analysis

Area of Science:

• Neuroscience
• Nephrology
• Genetics

Background:

• Growing evidence suggests links between neurological and renal systems.
• Understanding the causal relationship between brain activity and kidney disease is crucial.

Purpose of the Study:

• To investigate bidirectional causal relationships between resting-state functional brain activity and major kidney diseases.
• To explore the
• kidney-brain axis
• using Mendelian randomization.

Main Methods:

• Utilized genome-wide association study (GWAS) summary data for 191 resting-state fMRI (rs-fMRI) phenotypes.
• Analyzed GWAS data for seven kidney diseases from the FinnGen consortium and Kiryluk Lab.
• Employed inverse variance weighted (IVW) analysis, supplemented by MR-Egger, Weighted Median, Weighted Mode, and Robust Adjusted Profile Score (RAPS).

Main Results:

• Forward Mendelian randomization (MR) indicated that specific brain networks (central executive, default mode, limbic) influence susceptibility to kidney diseases.
• Reverse MR showed that chronic kidney disease (CKD) adversely affects brain functional networks involved in sensory-motor processing and cognitive integration.
• Observed modest effect sizes, but confirmed interlinked kidney disease and brain functional activity.

Conclusions:

• Evidence supports a bidirectional relationship between kidney diseases and resting-state brain activity.
• The identified
• kidney-brain axis
• may be relevant to renal and neurological pathophysiology.
• Findings align with clinical observations and emerging data on brain structural changes in CKD.