title: Head injury, potential interaction with genes, and risk for Parkinson's disease.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Our study suggests that head injury early in life may be an important risk factor for PD. The potential interaction with RBMS3 needs confirmation.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: gaojianjunxf@gmail.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: chenh2@niehs.nih.gov.
authors.forename: Honglei
authors.initials: H
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D006259:Craniocerebral Trauma / Q000209:etiology*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D015234:HLA-A Antigens; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Gene-environment interactions; Genome-wide association study; Head injury; Parkinson's disease