Gene-gene interactomes underlying major psychiatric disorders—what do we know?
Date of Issue2011
School of Biological Sciences
Institute of Mental Health
Psychiatric disorders such as schizophrenia and bipolar disorder are complex trait diseases in which there are potentially chronic debilitating consequences for the sufferer. There is mounting evidence implicating a wide variety of genes from dopaminergic to serotonin signalling pathways in disease neurobiology. In this systematic review, we seek to examine all existing empirical studies of gene-gene or epistatic interactions in SZ and BD. A synthesis of these data is significant for understanding potential candidate genes and their significant interactions with other genes, with the potential to improve our understanding of underlying neurobiological pathways and mechanisms with potential for novel therapeutic interventions in the future. We found a convergence of epistatic interactions in psychosis onto the cAMP-mediated signalling pathway. We also found that dopamine receptors have significant epistatic interactions with other genes but less so in single locus studies. Three gene-gene interactomes are found involving DISC1, ERBB4 and COMT. The AKT1-COMT interaction links the ERBB4 and COMT interactomes together. Replication studies still need to be done to validate epistatic interactions due to additive versus multiplicative effects and genetic heterogeneity and more work is needed to understand the relationships of such epistatic factors with clinical manifestations, neurocognitive and neuroanatomical measures within psychosis.
Final Year Project (FYP)
Nanyang Technological University