Coffee and Parkinson's disease: associations by CYP1A2 genotype and sex in UK Biobank.

Coffee consumption has been associated with Parkinson's disease (PD), but findings remain inconsistent. We examined whether this association differs by CYP1A2 genotype and sex in 435,551 UK Biobank participants free of PD at baseline. During a median follow-up of 15.7 years, 3319 incident PD cases were identified. In overall analyses, coffee intake was not associated with PD risk. However, coffee intake significantly interacted with CYP1A2 genotype. Among AA carriers, coffee intake below 5 cups/day was associated with lower PD risk (HR 0.83, 95% CI 0.74-0.93), and spline analyses indicated a nonlinear association with the lowest risk at around 3 cups/day. In contrast, high coffee intake (≥5 cups/day) was associated with higher PD risk in AC carriers (HR 1.43, 95% CI 1.11-1.85) and CC carriers (HR 1.84, 95% CI 1.08-3.11). Sex-stratified analyses showed that the inverse association in AA carriers was more evident in women, whereas increased risk at high intake among AC/CC carriers was mainly observed in men. These findings support heterogeneity in the association between coffee intake and PD risk according to CYP1A2 genotype.