Higher Coffee Consumption Is Associated With Reduced Cerebral Gray Matter Volume: A Mendelian Randomization Study

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Previous studies suggest coffee consumption's varied effects on neurological diseases.
• Two-sample Mendelian randomization (MR) studies indicate potential links between coffee and Alzheimer's disease, intracerebral hemorrhage, and stroke.
• The relationship between coffee intake and cerebral small vessel disease markers remains unclear.

Purpose of the Study:

• To investigate the causal effects of genetically predicted coffee consumption on magnetic resonance imaging (MRI) markers of cerebral small vessel disease.
• To examine the impact of genetically predicted coffee consumption on overall brain volume and specific brain region volumes.
• To utilize the two-sample MR method for robust causal inference.

Main Methods:

• Employed two-sample Mendelian randomization (MR) analysis.
• Utilized twelve single nucleotide polymorphisms (SNPs) as genetic instruments for daily coffee consumption (cups/day) in up to 375,833 individuals.
• Conducted replication analysis with four independent SNPs and multivariable analyses adjusting for risk factors.

Main Results:

• Genetically predicted coffee consumption (cups/day) showed a significant inverse association with gray matter volume (p=0.001).
• High coffee consumption was suggestively associated with decreased gray matter volume compared to low/no consumption (p=0.013).
• No significant causal effects were found for other MRI markers, including white matter hyperintensity, brain microbleeds, or total brain volume.

Conclusions:

• Genetically predicted higher coffee consumption is causally associated with reduced gray matter volume.
• Findings suggest a potential neurobiological impact of coffee consumption on brain structure.
• Further research is warranted to understand the mechanisms underlying this association.