Identification of genes related to mental disorders by text mining
MEDICINE
Authors: Wu, Ying; Dang, Meilin; Li, Hongxia; Jin, Xing; Yang, Wenxiao
Abstract
Mental disorders are important diseases with a high prevalence rate in the general population. Common mental disorders are complex diseases with high heritability, and their pathogenesis is the result of interactions between genetic and environmental factors. However, the relationship between mental disorders and genes is complex and difficult to evaluate. Additionally, some mental disorders involve numerous genes, and a single gene can also be associated with different types of mental disorders. This study used text mining (including word frequency analysis, cluster analysis, and association analysis) of the PubMed database to identify genes related to mental disorders. Word frequency analysis revealed 52 high-frequency genes important in studies of mental disorders. Cluster analysis showed that 5-HTT, SLC6A4, and MAOA are common genetic factors in most mental disorders; the intra-group genes in each cluster were highly correlated. Some mental disorders may have common genetic factors; for example, there may be common genetic factors between 'Affective Disorders' and 'Schizophrenia.' Association analysis revealed 35 frequent itemsets and 25 association rules, indicating close associations among genes. The results of association rules showed that CCK, MAOA, and 5-HTT are the most closely related. We used text mining technology to analyze genes related to mental disorders to further summarize and clarify the relationships between mental disorders and genes as well as identify potential relationships, providing a foundation for future experiments. The results of the associative analysis also provide a reference for multi-gene studies of mental disorders.
Constitutive Serotonin Transporter Reduction Resembles Maternal Separation with Regard to Stress-Related Gene Expression
ACS CHEMICAL NEUROSCIENCE
Authors: Comasco, Erika; Schijven, Dick; de Maeyer, Hanne; Vrettou, Maria; Nylander, Ingrid; Sundstrom-Poromaa, Inger; Olivier, Jocelien D. A.
Abstract
Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt(+/-) and 5-htt(+/+) male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt(+/+ )rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt(+/-) genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not groups except in non-maternally separated 5-htt(+/+) rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.