Bayesian sparse heritability analysis with high-dimensional neuroimaging phenotypes

Abstract

Heritability analysis plays a central role in quantitative genetics to describe genetic contribution to human complex traits and prioritize downstream analyses under large-scale phenotypes. Existing works largely focus on modeling single phenotype and currently available multivariate phenotypic methods often suffer from scaling and interpretation. In this article, motivated by understanding how genetic underpinning impacts human brain variation, we develop an integrative Bayesian heritability analysis to jointly estimate heritabilities for high-dimensional neuroimaging traits. To induce sparsity and incorporate brain anatomical configuration, we impose hierarchical selection among both regional and local measurements based on brain structural network and voxel dependence. We also use a nonparametric Dirichlet process mixture model to realize grouping among single nucleotide polymorphism-associated phenotypic variations, providing biological plausibility. Through extensive simulations, we show the proposed method outperforms existing ones in heritability estimation and heritable traits selection under various scenarios. We finally apply the method to two large-scale imaging genetics datasets: the Alzheimer's Disease Neuroimaging Initiative and United Kingdom Biobank and show biologically meaningful results.

Keywords: ADNI; Bayesian hierarchical selection; Dirichlet process; Heritability; Imaging genetics; Ising model; UK Biobank.

Figure 1

A demostration of the Bayesian sparse heritability analysis (BSHA) modeling framework.

Figure 2

ADNI data analysis results: estimated heritabilities under GCTA, MMHE, and BSHA over the whole brain. Only significant ones are represented by heatmaps from slides to in sagitall view, slides to in coronal view, and slides to in axial view with a 2-slide skipping.

Figure 3

UK Biobank data analysis results: the top row gives the orientation and location of white matter tracts in the brain; and Rows 2–4 and 5–7 display the estimated heritabilities under GCTA, GCTA (only significant voxels), and BSHA methods for FA and MD skeletons, respectively.