title: Apolipoprotein E controls the risk and age at onset of Parkinson disease.
abstract: BACKGROUND
  Similarities between Alzheimer disease (AD) and Parkinson disease (PD) suggest a possible role for apolipoprotein E (APOE) in PD. Most previous studies seeking to establish such a link used case-control datasets and results have been inconsistent.
  
  
  OBJECTIVE
  To investigate APOE's role in PD using family-based association analyses.
  
  
  METHODS
  APOE functional polymorphisms were genotyped for 658 PD affected families, including 282 multiplex and 376 singleton families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the effect of APOE on age at onset of PD.
  
  
  RESULTS
  APOE was significantly associated with risk of developing PD. Stratified analysis revealed that APOE was most strongly associated with families with a positive PD family history (global p = 0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a negative association of APOE-4 (p = 0.015) with age at onset in PD.
  
  
  CONCLUSIONS
  The APOE-4 allele increases risk and decreases age at onset of PD, an association that may not be dependent upon cognitive impairment.
authors.affiliation: Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA. yiju.li@duke.edu
authors.forename: Y J
authors.initials: YJ
authors.lastname: Li
authors.forename: M A
authors.initials: MA
authors.lastname: Hauser
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.forename: E R
authors.initials: ER
authors.lastname: Martin
authors.forename: M W
authors.initials: MW
authors.lastname: Booze
authors.forename: X J
authors.initials: XJ
authors.lastname: Qin
authors.forename: J W
authors.initials: JW
authors.lastname: Walter
authors.forename: M A
authors.initials: MA
authors.lastname: Nance
authors.forename: J P
authors.initials: JP
authors.lastname: Hubble
authors.forename: W C
authors.initials: WC
authors.lastname: Koller
authors.forename: R
authors.initials: R
authors.lastname: Pahwa
authors.forename: M B
authors.initials: MB
authors.lastname: Stern
authors.forename: B C
authors.initials: BC
authors.lastname: Hiner
authors.forename: J
authors.initials: J
authors.lastname: Jankovic
authors.forename: C G
authors.initials: CG
authors.lastname: Goetz
authors.forename: G W
authors.initials: GW
authors.lastname: Small
authors.forename: F
authors.initials: F
authors.lastname: Mastaglia
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: J M
authors.initials: JM
authors.lastname: Vance
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001315:Australia / Q000453:epidemiology; D003071:Cognition; D003704:Dementia / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D010375:Pedigree; D012306:Risk; D014481:United States / Q000453:epidemiology
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E