An exploratory analysis on gene-environment interactions for Parkinson disease.

Little is known about gene-environment interactions in Parkinson disease (PD). We examined potential interactions of smoking and caffeine intake with 10 genome-wide association studies single nucleotide polymorphisms (SNPs) at or near the SNCA, MAPT, LRRK2, and HLA loci among 584 PD patients and 1571 controls. The main effects of these SNPs and environmental exposures were consistent with previous reports. Family history of PD was associated with PD risk (odds ratio = 2.71, 95% confidence interval, 1.97-3.74), which was little affected by further adjustment for these SNPs and environmental exposures. Overall, we did not find significant interactions of either smoking or caffeine intake with these SNPs. However, with a combined smoking and caffeine intake exposure, we found a significant interaction with rs2896905 at SLC2A13, near LRRK2 (p uncorrected = 0.0008). Each A allele was associated with a 35% higher PD risk among never smokers with low caffeine intake, but with a 32% lower risk among smokers with high caffeine intake. This study provides preliminary evidence of a potential gene-environment interaction for PD, which should be investigated in future studies.