The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism

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• 作者：Eddie Stage^a ; ¹ ; Tugce Duran^a ; ¹ ; Shannon L. Risacher^b ; Naira Goukasian^c ; Triet M. Do^c ; John D. West^b ; Holly Wilhalme^d ; Kwangsik Nho^b ; Meredith Phillips^a ; David Elashoff^d ; Andrew J. Saykin^b ; ^d ; ^e ; ^f ; Liana G. Apostolova^a ; ^b ; ^c ; ^f ; ^{lapostol@iu.edu} ; for the Alzheimer's Disease Neuroimaging Initiative²
• 关键词：Genome-wide association studies (GWAS) ; Genetic variation ; Imaging genetics ; Magnetic resonance imaging (MRI) ; Fluorodeoxyglucose positron emission tomography (FDG PET) ; Atrophy ; Brain metabolism ; Risk genes ; ADNI ; Brain mapping ; Statistical parametric mapping (SPM) ; Positron emission tomography (PET) ; Alzheimer disease ; AD
• 刊名：Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
• 出版年：2016
• 出版时间：2016
• 年：2016
• 卷：5
• 期：Complete
• 页码：53-66
• 全文大小：2247 K
• 卷排序：5

文摘

We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism.MethodsWe 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, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8.ResultsSignificant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group.DiscussionMultiple 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.