Genetically predicted coffee consumption and amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Observational studies suggest a link between coffee consumption and amyotrophic lateral sclerosis (ALS).
• The causal relationship between coffee intake and ALS remains uncertain.

Purpose of the Study:

• To investigate the potential causal effect of coffee consumption on the risk of developing ALS using a Mendelian randomization approach.

Main Methods:

• Utilized genome-wide association study (GWAS) data for coffee consumption (n=129,422 and 375,833) to establish genetic instrumental variables.
• Employed summary-level data from a large ALS GWAS (20,806 cases, 59,804 controls) for the outcome analysis.
• Performed Mendelian randomization analyses with multiple genetic variants and sensitivity analyses to ensure robustness.

Main Results:

• Genetically predicted higher coffee consumption showed no statistically significant association with ALS risk.
• Odds ratios for high vs. infrequent/no coffee consumption, per 1-cup/day increase, and per 50% increase were consistently non-significant.
• Sensitivity analyses confirmed the absence of pleiotropic bias and heterogeneity, supporting the primary findings.

Conclusions:

• The Mendelian randomization study indicates that genetically predicted coffee consumption is not causally associated with amyotrophic lateral sclerosis.
• While observational studies suggest an association, this genetic analysis does not support a causal link.
• Further research is recommended to explore the impact of coffee consumption on ALS progression.