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Decision tree analysis of genetic risk for clinically heterogeneous Alzheimer's disease.


ABSTRACT: Heritability of Alzheimer's disease (AD) is estimated at 74% and genetic contributors have been widely sought. The ?4 allele of apolipoprotein E (APOE) remains the strongest common risk factor for AD, with numerous other common variants contributing only modest risk for disease. Variability in clinical presentation of AD, which is typically amnestic (AmnAD) but can less commonly involve visuospatial, language and/or dysexecutive syndromes (atypical or AtAD), further complicates genetic analyses. Taking a multi-locus approach may increase the ability to identify individuals at highest risk for any AD syndrome. In this study, we sought to develop and investigate the utility of a multi-variant genetic risk assessment on a cohort of phenotypically heterogeneous patients with sporadic AD clinical diagnoses.We genotyped 75 variants in our cohort and, using a two-staged study design, we developed a 17-marker AD risk score in a Discovery cohort (n?=?59 cases, n?=?133 controls) then assessed its utility in a second Validation cohort (n?=?126 cases, n?=?150 controls). We also performed a data-driven decision tree analysis to identify genetic and/or demographic criteria that are most useful for accurately differentiating all AD cases from controls.We confirmed APOE ?4 as a strong risk factor for AD. A 17-marker risk panel predicted AD significantly better than APOE genotype alone (P?

SUBMITTER: Yokoyama JS 

PROVIDER: S-EPMC4459447 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Decision tree analysis of genetic risk for clinically heterogeneous Alzheimer's disease.

Yokoyama Jennifer S JS   Bonham Luke W LW   Sears Renee L RL   Klein Eric E   Karydas Anna A   Kramer Joel H JH   Miller Bruce L BL   Coppola Giovanni G  

BMC neurology 20150328


<h4>Background</h4>Heritability of Alzheimer's disease (AD) is estimated at 74% and genetic contributors have been widely sought. The ε4 allele of apolipoprotein E (APOE) remains the strongest common risk factor for AD, with numerous other common variants contributing only modest risk for disease. Variability in clinical presentation of AD, which is typically amnestic (AmnAD) but can less commonly involve visuospatial, language and/or dysexecutive syndromes (atypical or AtAD), further complicate  ...[more]

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