Supplementary Material for: Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2

<i>Background and Purpose:</i> Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene <i>ADORA2A</i>) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: <i>CYP1A2</i>) metabolizes caffeine; thus, gene polymorphisms in <i>ADORA2A</i> and <i>CYP1A2</i> may influence the effect coffee consumption has on PD risk. <i>Methods:</i> In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in <i>ADORA2A</i> and <i>CYP1A2 </i>for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. <i>Results:</i> We estimated statistically significant interactions for <i>ADORA2A</i> rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], <i>p</i> = 0.02) but not prevalent PD. We did not observe interactions for <i>CYP1A2 </i>rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both <i>ADORA2A</i> and <i>CYP1A2</i>. <i>Conclusion:</i> We corroborated results from a previous report that described interactions between <i>ADORA2A </i>and<i> CYP1A2</i> polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases.