scholarly journals Identification and prioritization of gene sets associated with schizophrenia risk by co-expression network analysis in human brain

2018 ◽  
Vol 25 (4) ◽  
pp. 791-804 ◽  
Author(s):  
Eugenia Radulescu ◽  
Andrew E. Jaffe ◽  
Richard E. Straub ◽  
Qiang Chen ◽  
Joo Heon Shin ◽  
...  
2018 ◽  
Author(s):  
Eugenia Radulescu ◽  
Andrew E Jaffe ◽  
Richard E Straub ◽  
Qiang Chen ◽  
Joo Heon Shin ◽  
...  

AbstractSchizophrenia polygenic risk is plausibly manifested by complex transcriptional dysregulation in the brain, involving networks of co-expressed and functionally related genes. The main purpose of this study was to identify and prioritize co-expressed gene sets in a hierarchical manner, based on the strength of the relationships with clinical diagnosis and with the polygenic risk for schizophrenia. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to RNA-quality adjusted DLPFC RNA-Seq data from the LIBD Postmortem Human Brain Repository (90 controls, 74 schizophrenia; Caucasians) to construct co-expression networks and detect modules of co-expressed genes. After internal and external validation, modules of selected interest were tested for enrichment in biological ontologies, association with schizophrenia polygenic risk scores (PRS), with diagnosis and for enrichment in genes within the significant GWAS loci reported by the Psychiatric Genomic Consortium (PGC2). The association between schizophrenia genetic signals and modules of co-expression converged on one module showing a significant association with diagnosis, PRS and significant overlap with 36 PGC2 loci genes, deemed as tier 1 (strongest candidates for drug targets). Fifty-three PGC2 loci genes were in modules associated only with diagnosis (tier 2) and 59 in modules unrelated to diagnosis or PRS (tier 3). In conclusion, our study highlights complex relationships between gene co-expression networks in the brain and polygenic risk for SCZ and provides a strategy for using this information in selecting potentially targetable gene sets for therapeutic drug development.


2015 ◽  
Vol 57 (4) ◽  
pp. 580-594 ◽  
Author(s):  
Ahmed Mahfouz ◽  
Mark N. Ziats ◽  
Owen M. Rennert ◽  
Boudewijn P.F. Lelieveldt ◽  
Marcel J.T. Reinders

Author(s):  
Mingliang Wang ◽  
Jiashuang Huang ◽  
Mingxia Liu ◽  
Daoqiang Zhang

Brain network analysis can help reveal the pathological basis of neurological disorders and facilitate automated diagnosis of brain diseases, by exploring connectivity patterns in the human brain. Effectively representing the brain network has always been the fundamental task of computeraided brain network analysis. Previous studies typically utilize human-engineered features to represent brain connectivity networks, but these features may not be well coordinated with subsequent classifiers. Besides, brain networks are often equipped with multiple hubs (i.e., nodes occupying a central position in the overall organization of a network), providing essential clues to describe connectivity patterns. However, existing studies often fail to explore such hubs from brain connectivity networks. To address these two issues, we propose a Connectivity Network analysis method with discriminative Hub Detection (CNHD) for brain disease diagnosis using functional magnetic resonance imaging (fMRI) data. Specifically, we incorporate both feature extraction of brain networks and network-based classification into a unified model, while discriminative hubs can be automatically identified from data via ℓ1-norm and ℓ2,1-norm regularizers. The proposed CNHD method is evaluated on three real-world schizophrenia datasets with fMRI scans. Experimental results demonstrate that our method not only outperforms several state-of-the-art approaches in disease diagnosis, but also is effective in automatically identifying disease-related network hubs in the human brain.


Neuroreport ◽  
1996 ◽  
Vol 7 (10) ◽  
pp. 1597-1600 ◽  
Author(s):  
Jussi-Pekka Usenius ◽  
Sakari Tuohimetsä ◽  
Pauli Vainio ◽  
Mika Ala-Korpela ◽  
Yrjö Hiltunen ◽  
...  

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