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. 2015 Mar;21(3):292-6.
doi: 10.1016/j.parkreldis.2014.12.033. Epub 2015 Jan 8.

Head injury, potential interaction with genes, and risk for Parkinson's disease

Jianjun Gao  1 , Rui Liu  2 , Edward Zhao  2 , Xuemei Huang  3 , Michael A Nalls  4 , Andrew B Singleton  4 , Honglei Chen  5
Affiliations

Head injury, potential interaction with genes, and risk for Parkinson's disease

Jianjun Gao et al. Parkinsonism Relat Disord. 2015 Mar.

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.

Keywords: Gene-environment interactions; Genome-wide association study; Head injury; Parkinson's disease.

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Conflict of interest statement

Conflict of interest: None of the authors have financial conflict of interest for this work.

Figures

Figure 1
Figure 1
Number of head injuries before 1995 and PD risk after 1995. Odds ratio and 95% confidence interval (CI) were adjusted for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Sample sizes for analyses (cases/controls): no head injury: 418/1,169; 1 head injury: 64/130 ; two or more head injuries: 20/24. Five cases and 7 controls with head injuries did not provide information on the number of head injuries.
Figure 2
Figure 2
Year of first head injury before 1995 and PD risk after 1995. Odds ratio and 95% confidence interval (CI) were adjusted for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Sample sizes for analyses (cases/controls): no head injury: 418/1,169; before age 18: 41/55; age 18–<30: 24/47; age 30 and older: 17/50. Seven cases and 9 controls with head injuries did not provide information on the year of first head injury.
Figure 3
Figure 3
Potential interactions of head injury and RBMS3- rs10510622 on PD risk. Odds ratio and 95% confidence interval (CI) were adjusted for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Sample sizes for analyses (cases/controls): TT and no head injury: 279/757; TT and head injury: 45/123; CT/CC and no head injury: 126/372; CT/CC and head injury: 38/35.
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