Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

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Large-scale genetic studies of complex diseases such as schizophrenia have identified a variety of susceptibility loci. Since many of the respective variants have only a weak influence on disease risk, pathophysiological interpretation of the results is problematic. Investigation of the joint effects of multiple functionally related genes or pathways increases the power to detect disease related genes, and provides insights into the etiology of the disease in question. In the present study, an integrated hierarchical approach was applied to: (i) identify pathways associated with complex neuropsychiatric disease schizophrenia (ii) detect potentially affected genes in these pathways; and (iii) annotate the functional consequences of genetic markers in the affected genes or their regulatory regions. Two samples comprising >10,000 individuals of European ancestry as well as data from the Psychiatric Genomics Consortium schizophrenia study were examined. Pathways representing transcriptional regulation and gene expression, cell adhesion, apoptosis, and synapse organization showed significant association with schizophrenia. In particular, CTCF, CACNB2, and ARL5B, i.e. genes involved in chromatin modulation, calcium channel signaling and membrane transport, respectively, were highlighted as candidate genes for schizophrenia risk.

Vyšlo v časopise: Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004345
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004345

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