The Contribution Plot: Decomposition and Graphical Display of the RV Coefficient, with Application to Genetic and Brain Imaging Biomarkers of Alzheimer’s Disease

Background/Aims: Alzheimer’s disease (AD) is a chronic neurodegenerative disease that causes memory loss and a decline in cognitive abilities. AD is the sixth leading cause of death in the USA, affecting an estimated 5 million Americans. To assess the association between multiple genetic variants and multiple measurements of structural changes in the brain, a recent study of AD used a multivariate measure of linear dependence, the RV coefficient. The authors decomposed the RV coefficient into contributions from individual variants and displayed these contributions graphically. Methods: We investigate the properties of such a “contribution plot” in terms of an underlying linear model, and discuss shrinkage estimation of the components of the plot when the correlation signal may be sparse. Results: The contribution plot is applied to simulated data and to genomic and brain imaging data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Conclusions: The contribution plot with shrinkage estimation can reveal truly associated explanatory variables.

[1]  C. Dyck,et al.  Alzheimer's & Dementia: The Journal of the Alzheimer's Association , 2020, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[2]  JinCheol Choi Decomposing the RV coefficient to identify genetic markers associated with changes in brain structure , 2018 .

[3]  Wei Pan,et al.  Adaptive testing for association between two random vectors in moderate to high dimensions , 2017, Genetic epidemiology.

[4]  Alzheimer’s Association 2017 Alzheimer's disease facts and figures , 2017, Alzheimer's & Dementia.

[5]  Mitchell J. Machiela,et al.  LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants , 2015, Bioinform..

[6]  Elena Kaarina Szefer,et al.  Joint analysis of imaging and genomic data to identify associations related to cognitive impairment , 2014 .

[7]  Yanyan Li,et al.  NEDD9 rs760678 polymorphism and the risk of Alzheimer's disease: A meta-analysis , 2012, Neuroscience Letters.

[8]  Mark E. Schmidt,et al.  The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception , 2012, Alzheimer's & Dementia.

[9]  C. Jack,et al.  Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans , 2010, Alzheimer's & Dementia.

[10]  M. Wolfson,et al.  NEDD9 promotes oncogenic signaling in mammary tumor development. , 2009, Cancer research.

[11]  T. Vogel,et al.  Transforming Growth Factor β Promotes Neuronal Cell Fate of Mouse Cortical and Hippocampal Progenitors In Vitro and In Vivo: Identification of Nedd9 as an Essential Signaling Component , 2009, Cerebral cortex.

[12]  R. Tibshirani,et al.  A penalized matrix decomposition, with applications to sparse principal components and canonical correlation analysis. , 2009, Biostatistics.

[13]  D. Tritchler,et al.  Sparse Canonical Correlation Analysis with Application to Genomic Data Integration , 2009, Statistical applications in genetics and molecular biology.

[14]  R. Buckner,et al.  The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals , 2008, Cerebral cortex.

[15]  Y. Escoufier LE TRAITEMENT DES VARIABLES VECTORIELLES , 1973 .

[16]  D. Horvitz,et al.  A Generalization of Sampling Without Replacement from a Finite Universe , 1952 .

[17]  H. Hotelling Relations Between Two Sets of Variates , 1936 .

[18]  M. Beg,et al.  Alzheimer ’ s Disease Neuroimaging Initiativea Multivariate association between single-nucleotide polymorphisms in Alzgene linkage regions and structural changes in the brain : discovery , refinement and validation , 2017 .

[19]  S. Holmes,et al.  Measuring multivariate association and beyond. , 2016, Statistics surveys.

[20]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[21]  Shannon L. Risacher,et al.  Identifying quantitative trait loci via group-sparse multitask regression and feature selection: an imaging genetics study of the ADNI cohort , 2012, Bioinform..