Genome-wide association studies of brain imaging data via weighted distance correlation

Imaging genetics is mainly used to reveal the pathogenesis of neuropsychiatric risk genes and understand the relationship between human brain structure, functional and individual differences. Increasingly, the brain-wide imaging phenotypes in voxels are available to test the association with genetic markers. A challenge with analyzing such data is their high dimensionality and complex relationships.

To tackle this challenge, we introduce a weighed distance correlation (wdCor) that can assess the association between genetic markers and voxel-based imaging data. Importantly, the wdCor test takes the voxel-based data as a whole multivariate phenotype, which preserves the spatial continuity and might enhance the power. Besides, an adaptive permutation procedure is introduced to determine the P-values of the wdCor test and also alleviate the computational burden in GWAS. In extensive simulation studies, wdCor achieves much better performances compared to the original distance correlation. We also successfully apply wdCor to conduct a large-scale analysis on data from the Alzheimer's disease neuroimaging project (ADNI).

Our wdCor method provides new research directions and ideas for multivariate analysis of high-dimensional data, it can also be used as a tool for scientific analysis of imaging genetics research in practical applications. The R package wdcor, and the code for reproducing all results in this article is available in Github: https://github.com/yangyuhui0129/wdcor.

Supplementary data are available at Bioinformatics online.