It has been widely shown that genomic factors influence both risk for schizophrenia and variation in functional brain connectivity. Moreover, schizophrenia is characterized by disrupted brain connectivity. In this work, we proposed a genome-connectome bipartite graph model to perform imaging genomic analysis. Functional network connectivity (FNC) was estimated after decomposing resting state functional magnetic resonance imaging data from both healthy controls (HC) and patients with schizophrenia (SZ) into spatial brain components using group independent component analysis (G-ICA). Then 83 FNC connections showing a group difference (HC vs SZ) were selected as fMRI nodes, and eighty-one schizophrenia-related single nucleotide polymorphisms (SNPs) were selected as genetic nodes respectively in the bipartite graph. Edges connecting pairs of genetic and fMRI nodes were defined based on the SNP-FNC associations across subjects evaluated by a general linear model. Results show that some SNP nodes in the bipartite graph have a high degree implying they are influential in modulating brain connectivity and may be more strongly associated with the risk of schizophrenia than other SNPs. A bi-clustering analysis detected a cluster with 15 SNPs interacting with 38 FNC connections, most of which were within or between somato-motor and visual brain areas. This suggests that the activity of these brain regions may be related to common SNPs and provides insights into the pathology of schizophrenia. The findings suggest that the SNP-FNC bipartite graph approach is a novel model to investigate genetic influences on functional brain connectivity in mental illness.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (NIH) grants including a COBRE grant ( P20GM103472/5P20RR021938 ), R01 grants ( R01EB005846 , 1R01EB006841 , 1R01DA040487 , R01REB020407 , R01EB000840 , and R37MH43775 ) and the National Science Foundation (NSF) grants #1539067 , #1618551 and #1631838 . This work was also supported by the National Center for Research Resources at the National Institutes of Health , grant numbers: NIH 1 U24 RR021992 (Function Biomedical Informatics Research Network), NIH 1 U24 RR025736-01 (Biomedical Informatics Research Network Coordinating Center). This work was partly supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDBS03040100), Brain Initiative of Beijing City (Z181100001518005) Chinese NSF (81471367, 61773380, PI: Sui J; 61703253, PI: YHD) and Natural Science Foundation of Shanxi (2016021077, PI: YHD).”
- Bipartite graph