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

Maria Vounou, Eva Janousova, Robin Wolz, Jason L Stein, Paul M Thompson, Daniel Rueckert, Giovanni Montana, Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

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.
Original languageEnglish
Article numberN/A
Pages (from-to)700-716
Number of pages17
JournalNeuroImage
Volume60
Issue number1
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Algorithms
  • Alzheimer Disease
  • Female
  • Genome-Wide Association Study
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Neuroimaging
  • Phenotype

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