Identifying imaging genetic associations via regional morphometricity estimation

Published in PSB, 2022

Citation: Jingxuan Bao, Zixuan Wen, Mansu Kim, Andrew J. Saykin, Paul M. Thompson, Yize Zhao, Li Shen, and for the Alzheimer’s Disease Neuroimaging Initiative. (2021). "Identifying imaging genetic associations via regional morphometricity estimation." Pacific Symposium on Biocomputing.

## Abstract Brain imaging genetics is an emerging research field aiming to reveal the genetic basis of brain traits captured by imaging data. Inspired by heritability analysis, the concept of morphometricity was recently introduced to assess trait association with whole brain morphology. In this study, we extend the concept of morphometricity from its original definition at the whole brain level to a more focal level based on a region of interest (ROI). We propose a novel framework to identify the SNP-ROI association via regional morphometricity estimation of each studied single nucleotide polymorphism (SNP). We perform an empirical study on the structural MRI and genotyping data from a landmark Alzheimer’s disease (AD) biobank; and yield promising results. Our findings indicate that the AD-related SNPs have higher overall regional morphometricity estimates than the SNPs not yet related to AD. This observation suggests that the variance of AD SNPs can be explained more by regional morphometric features than non-AD SNPs, supporting the value of imaging traits as targets in studying AD genetics. Also, we identified 11 ROIs, where the AD/non-AD SNPs and significant/insignificant morphometricity estimation of the corresponding SNPs in these ROIs show strong dependency. Supplementary motor area (SMA) and dorsolateral prefrontal cortex (DPC) are enriched by these ROIs. Our results also demonstrate that using all the detailed voxel-level measures within the ROI to incorporate morphometric information outperforms using only a single average ROI measure, and thus provides improved power to detect imaging genetic associations. Jingxuan Bao, Zixuan Wen, Mansu Kim, Andrew J. Saykin, Paul M. Thompson, Yize Zhao, Li Shen, and for the Alzheimer’s Disease Neuroimaging Initiative. (2021). "Identifying imaging genetic associations via regional morphometricity estimation." Pacific Symposium on Biocomputing. [Manuscript](http://psb.stanford.edu/psb-online/proceedings/psb22/bao_morphometricity.pdf)