In 435,551 UK Biobank participants followed for a median of 15.7 years, overall coffee consumption was not associated with Parkinson’s disease risk, but the relationship differed significantly according to CYP1A2 genotype. Lower risk was observed with low-to-moderate coffee intake among fast-metabolizer AA carriers, while higher intake was associated with increased risk among AC and CC carriers, although the observational findings do not establish causality and sex-specific patterns require cautious interpretation.