Network-based investigation of genetic modules associated with functional brain networks in schizophrenia

Abstract

We developed a new sparse multivariate regression method, collaborative sparse reduced rank regression(C-sRRR) for detecting genetic networks associated with brain functional networks in schizophrenia (SZ). Our study: 1) introduced both genetic and brain network structure to group single nucleotide polymorphism (SNP) and voxels simultaneously for utilizing the interacting effects implied in both features; 2) used collaborative sparse group lasso to perform genetic variants selection and nuclear norm penalty to address the interrelationship among voxels; 3) developed an efficient algorithm for solving the non-smooth optimization. In real data analysis, we constructed 8605 genetic sub-networks (modules) from 722177 SNPs with a median module size of 9. A functional brain network was extracted which also showed significant discriminative characteristics between SZ and healthy controls. A sub sampling strategy was applied to identify 57 highly ranked genes from 14 high-ranking modules. 14 of them are SZ susceptibility genes and 6 genes were consistent with the findings in previous study.