Title
Improving mass-univariate analysis of neuroimaging data by modelling important unknown covariates: Application to Epigenome-Wide Association Studies.
Abstract
Statistical inference on neuroimaging data is often conducted using a mass-univariate model, equivalent to fitting a linear model at every voxel with a known set of covariates. Due to the large number of linear models, it is challenging to check if the selection of covariates is appropriate and to modify this selection adequately. The use of standard diagnostics, such as residual plotting, is clearly not practical for neuroimaging data. However, the selection of covariates is crucial for linear regression to ensure valid statistical inference. In particular, the mean model of regression needs to be reasonably well specified. Unfortunately, this issue is often overlooked in the field of neuroimaging. This study aims to adopt the existing Confounder Adjusted Testing and Estimation (CATE) approach and to extend it for use with neuroimaging data. We propose a modification of CATE that can yield valid statistical inferences using Principal Component Analysis (PCA) estimators instead of Maximum Likelihood (ML) estimators. We then propose a non-parametric hypothesis testing procedure that can improve upon parametric testing. Monte Carlo simulations show that the modification of CATE allows for more accurate modelling of neuroimaging data and can in turn yield a better control of False Positive Rate (FPR) and Family-Wise Error Rate (FWER). We demonstrate its application to an Epigenome-Wide Association Study (EWAS) on neonatal brain imaging and umbilical cord DNA methylation data obtained as part of a longitudinal cohort study. Software for this CATE study is freely available at http://www.bioeng.nus.edu.sg/cfa/Imaging_Genetics2.html.
Year
DOI
Venue
2018
10.1016/j.neuroimage.2018.01.073
NeuroImage
Keywords
Field
DocType
Univariate analysis,Unknown covariates,Non-parametric testing,Epigenetics,Neonatal brain
False positive rate,Covariate,Linear model,Psychology,Cognitive psychology,Parametric statistics,Statistical inference,Artificial intelligence,Statistical hypothesis testing,Machine learning,Estimator,Linear regression
Journal
Volume
ISSN
Citations 
173
1053-8119
0
PageRank 
References 
Authors
0.34
5
9
Name
Order
Citations
PageRank
Bryan Guillaume100.34
Changqing Wang200.34
Joann S Poh310.68
Mo Jun Shen400.34
Mei Lyn Ong500.34
Pei Fang Tan600.34
Neerja Karnani700.34
Michael J Meaney8223.47
Anqi Qiu957138.34