title: Genetic risk and age in Parkinson's disease: Continuum not stratum.
abstract: BACKGROUND
  Recent genomewide association study meta-analyses have identified 28 loci associated with risk of Parkinson's disease (PD). We sought to investigate whether these genetic risk factors are associated with PD age at onset.
  
  
  METHODS
  Genetic risk scores from these loci were calculated for 6,249 cases. Linear regression tested associations between cumulative genetic risk and PD age at onset.
  
  
  RESULTS
  Increasing genetic risk scores were associated with earlier age at onset (beta = -0.10, P = 2.92 × 10(-8) , adjusted r(2)  = 0.27). Single standard deviation increase in genetic risk score is associated with 37.44 d earlier age at onset. Highest genetic risk was found at 31 to 60 y, onset slightly below average age at onset (AAO).
  
  
  CONCLUSIONS
  Common genetic risk factors have a small but consistent association with AAO in PD.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mike A
authors.initials: MA
authors.lastname: Nalls
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Escott-Price
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK.
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Williams
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, England, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Lubbe
authors.affiliation: Merck Research Laboratories, Cambridge, Massachusetts, USA.
authors.forename: Margaux F
authors.initials: MF
authors.lastname: Keller
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, England, UK.
authors.forename: Huw R
authors.initials: HR
authors.lastname: Morris
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
keywords: Parkinson's disease; age at onset; genetics; statistics