Genetics and Epigenetics of Schizophrenia

Abstract

Schizophrenia (SCZ) is a complex mental disorder, with a longstanding history of neurobiological investigation. It is more common in those persons who are genetically predisposed to the disorder. Since Kraepelin, psychiatrists were aware that the SCZ tended to run in families. Its heritability is up to 85%. Although the etiology of SCZ is unknown, it is now thought to be multifactorial, with multiple susceptibility genes interacting with environmental and developmental factors. There is a huge amount of genetic studies, including polymorphisms, expression, methylation, microRNAs, and epigenomics. However, identifying genes for SCZ using traditional genetic approaches has thus far proven quite difficult. Reasons for this include the complexity, heterogeneity, and comorbidity of this disorder, and also the poor definition of the clinical phenotype. Important approaches to find the relation between genotype and phenotype and may be causal genetic factors are endophenotypes and pathway analysis. However, genetic researchers need to consider carefully the models of causality they choose. There is a pathophysiological pathway that extends from genes, through proteins, neurons, neural circuits, neural regions, mental functions, external behaviors, and symptoms of SCZ. In this chapter, the genetics and epigenetics of SCZ are briefly discussed.

Epigenetics and Genetics of Schizophrenia

“…This suggests that increasing the sample size in analysis can help to detect more risk variants. (Ananloo, 2018) The analysis of a European ancestry sample GWAS and then through a replication study, found notable associations for seven loci, including 1p21.3, 2q32.3, 6p21.32-p22.1, 8p23.2, 8q21.3, 10q24.32-q24.33, and 18q21.2 with schizophrenia. The most impactful finding was with a miRNA-137 SNP.…”

“…According to published genetic association studies of schizophrenia, it has been reported that across 118 meta-analyses, 16 genes, consisting of APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1 showed significant effects. (Ananloo, 2018) Genome-wide association studies is an approach that rapidly scans genetic variants across various peoples' genomes to find variations that are associated with a particular trait or disease. By utilizing this approach, researchers are able to use the information to create and develop improved hypotheses to treat, detect and prevent the disease.…”

“…In a meta-analysis of 18 genome-wide association studies and a replication study, TCF4, NOTCH4, POM121L2, AS3MT, CNNM2, and NT5C2 genes were found to have a significant association with schizophrenia. (Ananloo, 2018)…”

“…However, the probability of developing it for someone with one parent with the mental disorder is 17% and for someone whose parents both have the mental disorder is 46%. (Ananloo, 2018) Mutations and alterations of various genes can make people exceedingly more susceptible to getting schizophrenia. The treatments for schizophrenia that are currently being used in practice attempt to treat the symptoms of the mental disorder and reduce their impact on the affected person's life.…”