@article{75df139826bf4507b77bc72d5a0aee4b,
title = "Sparse reduced-rank regression detects genetic associations with voxel-wise longitudinal phenotypes in Alzheimer's disease",
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.",
author = "Maria Vounou and Eva Janousova and Robin Wolz and Stein, {Jason L.} and Thompson, {Paul M.} and Daniel Rueckert and Giovanni Montana",
note = "Funding Information: Maria Vounou is supported by a grant from the EPSRC and GlaxoSmithKline Clinical Imaging Center . This work was also partly funded by the European Union 7th Framework Program, PredictAD, From Patient Data to Personalised Healthcare in Alzheimer's Disease . Imaging data was provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Abbott , AstraZeneca AB , Bayer Schering Pharma AG , Bristol-Myers Squibb , Eisai Global Clinical Development , Elan Corporation , Genentech , GE Healthcare , GlaxoSmithKline , Innogenetics , Johnson and Johnson , Eli Lilly and Co. , Medpace, Inc. , Merck and Co., Inc. , Novartis AG , Pfizer Inc , F. Hoffman-La Roche , Schering-Plough , Synarc, Inc. , and Wyeth , as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation , with participation from the U.S. Food and Drug Administration . Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education , and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. ",
year = "2012",
month = mar,
doi = "10.1016/j.neuroimage.2011.12.029",
language = "English",
volume = "60",
pages = "700--716",
journal = "NeuroImage",
issn = "1053-8119",
publisher = "Academic Press Inc.",
number = "1",
}