An Exploratory Analysis on Gene-Environment Interactions for Parkinson Disease (PD4.003)

Objective: To explore potential interactions between variations of Parkinson disease (PD) susceptibility genes with smoking and caffeine intake. Background Gene-environment interaction is critical to understanding the etiology of PD. Little, however, is known about whether PD susceptibility genes interact with known environmental risk factors for PD. Design/Methods: We examined potential interactions of prospectively collected data on smoking and caffeine intake with several PD susceptible SNPs selected from previous GWAS, among 584 non-Hispanic Caucasian cases and 1,571 controls. Genotyping data were primarily from the replication sample of a previous GWAS study, and we focused on ten tag SNPs at or flanking the SNCA, MAPT, LRRK2 and HLA-DRA loci. Results: The main effects of PD susceptibility loci and environmental exposures were consistent with previous reports. Family history was also associated with PD risk (OR=2.71, 95% CI: 1.97 3.37), which was little affected after further adjusting 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 exposure, we found a significant interaction with rs2896905 near the LRRK2 gene (uncorrected p = 0.0008), which remained statistically significant even after Bonferroni correction. Each A allele was associated with a 35% higher PD risk (OR=1.35, 95% CI: 1.01 – 1.82, p = 0.04) among never smokers with low caffeine intake, but with a 32% lower PD risk (OR=0.68, 95% CI: 0.51 – 0.90, p = 0.007) among smokers with high caffeine intake. Conclusions: This study provides preliminary evidence that smoking and caffeine intake may modify the association of rs2896905 with PD, which should be confirmed and investigated in future studies. Supported by: The intramural research program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), the National Cancer Institute (Z01 CP010196-02), and a NIH extramural grant (R01 NS060722) to Dr Huang. Disclosure: Dr. Gao has nothing to disclose. Dr. Nalls has nothing to disclose. Dr. Shi has nothing to disclose. Dr. Joubert has nothing to disclose. Dr. Hernandez has nothing to disclose. Dr. Huang has nothing to disclose. Dr. Hollenbeck has nothing to disclose. Dr. Singleton has nothing to disclose. Dr. Chen has nothing to disclose.