The impact of drugs of abuse on the development of mental disorders: a gene-environment interaction study

• Grant number: 23/05775-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcos Leite Santoro
• Grantee: Pedro Henrique Destro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Mental disorders are one of the leading causes of years of life lost due to disability. Psychiatric symptoms usually begin during adolescence and may progress and persist into adulthood. Despite advances and investments, Genome Wide Association Studies (GWAS) are only able to explain 1/4 of the total heritability, and it is believed that the remaining heritability may be explained by gene-gene and gene-environment interactions, as well as other variants not studied in GWAS. As multifactorial phenotypes, both genetic variants and environmental factors play a role in determining an individual's characteristics, including the development of mental disorders such as depression, schizophrenia, and bipolar disorder, suggesting that while genetic factors may make a person more susceptible to these conditions, the interplay between genomics and their environmental exposure to stressors contributes to the development of the disorder. Among environmental factors, the current project highlights the use of drugs of abuse in the establishment of mental disorders, an active but complex and not fully understood area of research. Thus, this study aims to relate genetic variants associated with drug use that increase the risk of incidence of mental disorders in 2190 individuals from a Brazilian high-risk cohort for mental disorders, the Brazilian High Risk Cohort Study (BHRCS), which has 13 years of data collected in three phases. This will be accomplished by surveying these variants in the literature, followed by verifying the presence of the variants in the genomic data of BHRCS individuals directly and indirectly using bioinformatics tools such as PLINK and RStudio. Thus, it is expected that individuals in the cohort who have risk variants associated with drug use and who have used these substances will be more likely to develop mental disorders than those who have not used the substances and/or do not have the analyzed risk variants, corroborating the hypothesis that gene-environment interaction influences the development of mental disorders and contributing to other ongoing studies that jointly evaluate data from neuroimaging, genetic risk, environmental risk, among others.