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PMID: 22209813 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sparse reduced-rank regression detects genetic associations with voxel-wise longitudinal phenotypes in Alzheimer's disease.

NeuroImage ·Vol. 60 ·No. 1 ·2012-03-00 ·Pages 700-16

Vounou M, Janousova E, Wolz R, Stein JL, Thompson PM, Rueckert D, Montana G, Alzheimer's Disease Neuroimaging Initiative

Abstract

Scanning the entire genome in search of variants related to imaging phenotypes holds great promise in elucidating the genetic etiology of neurodegenerative disorders. Here we discuss the application of a penalized multivariate model, sparse reduced-rank regression (sRRR), for the genome-wide detection of markers associated with voxel-wise longitudinal changes in the brain caused by Alzheimer's disease (AD). Using a sample from the Alzheimer's Disease Neuroimaging Initiative database, we performed three separate studies that each compared two groups of individuals to identify genes associated with disease development and progression. For each comparison we took a two-step approach: initially, using penalized linear discriminant analysis, we identified voxels that provide an imaging signature of the disease with high classification accuracy; then we used this multivariate biomarker as a phenotype in a genome-wide association study, carried out using sRRR. The genetic markers were ranked in order of importance of association to the phenotypes using a data re-sampling approach. Our findings confirmed the key role of the APOE and TOMM40 genes but also highlighted some novel potential associations with AD.

MeSH Terms
Algorithms Alzheimer Disease/genetics,pathology Female Genome-Wide Association Study Humans Image Processing, Computer-Assisted Male Neuroimaging Phenotype
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Vounou Maria
Statistics Section, Department of Mathematics, Imperial College London, UK.
Janousova Eva
Wolz Robin
Stein Jason L
Thompson Paul M
Rueckert Daniel
Montana Giovanni
Alzheimer's Disease Neuroimaging Initiative
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Article Info
Journal
NeuroImage
Abbr.
Neuroimage
ISSN
1095-9572
DOI
10.1016/j.neuroimage.2011.12.029
Published
2012-03-00
Epub
2011-00-22
Pages
700-16
Language
English
Region
United States
NLM ID
9215515
PMCID
PMC3551466
Subset
IM
Grants
NIA NIH HHS · R01 AG040060 · United States
NIA NIH HHS · U01 AG024904 · United States
External Links
PubMed source DOI: 10.1016/j.neuroimage.2011.12.029 PMC Full Text View journal details
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