EQTL (expression quantitative trait loci) identification and characterization of a gene expression profile in children and adolescents at risk for mental disorders

Abstract

Neuropsychiatric disorders are the main cause of years lost because of disability in the worldwide young people. Many of these disorders present a high heritability, reaching 60-80% for schizophrenia and bipolar disorder. This suggests that the genome contains a large amount of information with a diagnosis potential. However, polygenic nature of these diseases, added to the influence of environmental factors makes it difficult to explore this information. Mental disorders and early environmental factors (such as neglect and abuse) appear to alter the expression of certain genes, as well as genetic variants (by expression quantitative trait loci (eQTL)). The aim of this study is to identify gene expression changes in children and adolescents with genetic and clinical risk for mental disorders. For this we will select 100 children with: 1) higher symptoms of psychopathology, measured by the Child Behavior Checklist (CBCL); 2) history of abuse (neglect, emotional, physical or sexual) and / or obstetric risk factors; 3) increased genetic risk, suggested by family history for mental disorders; and 100 control children with lower scores for these three items and no psychiatric diagnosis. For the 200 selected samples we will be perform microarray expression (GeneChip® Human Gene 1.0 ST Array) and genome-wide genotyping using Infinum® HumanCore Array. We will compare the two groups in order to identify a expression profile for risk for mental disorders; environmental factors that alter gene expression and genetic variants that change these profiles by eQTLs analysis. We intend to help identify risk factors for mental disorders in order to act in the early prevention and diagnosis. (AU)