title: The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism.
abstract: BACKGROUND
  We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism.
  
  
  METHODS
  We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, andAPOEε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8.
  
  
  RESULTS
  Significant predictors of brain GMD wereSLC24A4/RIN3in the pooled and mild cognitive impairment (MCI);ZCWPW1in the MCI; andABCA7,EPHA1, andINPP5Din the AD groups. Significant predictors of hypometabolism wereEPHA1in the pooled, andSLC24A4/RIN3, NME8, andCD2APin the normal control group.
  
  
  CONCLUSIONS
  Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Eddie
authors.initials: E
authors.lastname: Stage
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tugce
authors.initials: T
authors.lastname: Duran
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Risacher
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Naira
authors.initials: N
authors.lastname: Goukasian
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Triet M
authors.initials: TM
authors.lastname: Do
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: West
authors.affiliation: Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Wilhalme
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kwangsik
authors.initials: K
authors.lastname: Nho
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Phillips
authors.affiliation: Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Indiana University Network Science Institute, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Liana G
authors.initials: LG
authors.lastname: Apostolova
keywords: AD; ADNI; Alzheimer disease; Atrophy; Brain mapping; Brain metabolism; Fluorodeoxyglucose positron emission tomography (FDG PET); Genetic variation; Genome-wide association studies (GWAS); Imaging genetics; Magnetic resonance imaging (MRI); Positron emission tomography (PET); Risk genes; Statistical parametric mapping (SPM)