Abstract
INTRODUCTION: To evaluate the association between head injury and Parkinson's disease (PD), focusing on the timing of head injury, and to explore potential interactions between head injury and genetic factors in PD etiology. METHODS: The analysis included 507 PD cases and 1330 controls, all non-Hispanic Whites. Head injury was retrospectively asked, and genotyping was performed mainly as part of a previous GWAS. RESULTS: We found a positive association between head injury and PD risk. Compared with no previous head injury, the odds ratio (OR) was 1.39 (95% confidence interval [CI]: 1.00, 1.94) for one and 2.33 (95% CI: 1.25, 4.35) for two or more head injuries (P for trend = 0.0016). We further found that the higher risk was largely attributed to head injuries before age 30. Compared with no previous head injury, the OR was 2.04 (95% CI: 1.33, 3.14) for head injury that occurred before age 18, 1.39 (95% CI: 0.81, 2.36) for head injury between ages 18-<30, and 1.04 (95% CI: 0.58, 1.87) for head injury that occurred at age 30 or older (P for trend = 0.001). Exploratory interaction analyses showed a significant interaction between head injury and a SNP at the RBMS3 locus (rs10510622, uncorrected P = 0.0001). No interaction was found with GWAS tag SNPs at or near the MAPT, SNCA, LRRK2, and HLA loci. CONCLUSION: Our study suggests that head injury early in life may be an important risk factor for PD. The potential interaction with RBMS3 needs confirmation.