TY - JOUR
T1 - Predicting Alzheimer's disease using combined imaging-whole genome SNP data
AU - Kong, Dehan
AU - Giovanello, Kelly S.
AU - Wang, Yalin
AU - Lin, Weili
AU - Lee, Eunjee
AU - Fan, Yong
AU - Murali Doraiswamy, P.
AU - Zhu, Hongtu
N1 - Publisher Copyright:
© 2015-IOS Press and the authors. All rights reserved.
PY - 2015/6/25
Y1 - 2015/6/25
N2 - The growing public threat of Alzheimer's disease (AD) has raised the urgency to discover and validate prognostic biomarkers in order to predicting time to onset of AD. It is anticipated that both whole genome single nucleotide polymorphism (SNP) data and high dimensional whole brain imaging data offer predictive values to identify subjects at risk for progressing to AD. The aim of this paper is to test whether both whole genome SNP data and whole brain imaging data offer predictive values to identify subjects at risk for progressing to AD. In 343 subjects with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI-1), we extracted high dimensional MR imaging (volumetric data on 93 brain regions plus a surface fluid registration based hippocampal subregion and surface data), and whole genome data (504,095 SNPs from GWAS), as well as routine neurocognitive and clinical data at baseline. MCI patients were then followed over 48 months, with 150 participants progressing to AD. Combining information from whole brain MR imaging and whole genome data was substantially superior to the standard model for predicting time to onset of AD in a 48-month national study of subjects at risk. Our findings demonstrate the promise of combined imaging-whole genome prognostic markers in people with mild memory impairment.
AB - The growing public threat of Alzheimer's disease (AD) has raised the urgency to discover and validate prognostic biomarkers in order to predicting time to onset of AD. It is anticipated that both whole genome single nucleotide polymorphism (SNP) data and high dimensional whole brain imaging data offer predictive values to identify subjects at risk for progressing to AD. The aim of this paper is to test whether both whole genome SNP data and whole brain imaging data offer predictive values to identify subjects at risk for progressing to AD. In 343 subjects with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI-1), we extracted high dimensional MR imaging (volumetric data on 93 brain regions plus a surface fluid registration based hippocampal subregion and surface data), and whole genome data (504,095 SNPs from GWAS), as well as routine neurocognitive and clinical data at baseline. MCI patients were then followed over 48 months, with 150 participants progressing to AD. Combining information from whole brain MR imaging and whole genome data was substantially superior to the standard model for predicting time to onset of AD in a 48-month national study of subjects at risk. Our findings demonstrate the promise of combined imaging-whole genome prognostic markers in people with mild memory impairment.
KW - Alzheimer's disease
KW - genetics
KW - magnetic resonance imaging
KW - proportional hazards models
KW - risk
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U2 - 10.3233/JAD-150164
DO - 10.3233/JAD-150164
M3 - Article
C2 - 25869783
AN - SCOPUS:84934271687
SN - 1387-2877
VL - 46
SP - 695
EP - 702
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 3
ER -