Identification of copy number variations (CNVs) in a cohort of children and adolescents with high risk for psychiatric disorders

• Grant number: 21/04591-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2021
• Effective date (End): December 31, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcos Leite Santoro
• Grantee: Júlia Arendt Antonieto
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Mental disorders are considered to be one of the main causes of years lost due to disability. Symptoms usually begin during childhood and adolescence and can progress and persist into adulthood. Mental disorders are multifactorial and very polygenic disorders. In addition to the contribution of common genetic variants, other studies have shown that rare variants, with high effect size and penetrance, such as copy number variations (CNV), are present in the pathogenicity of mental disorders. In this study, we aimed to identify pathogenic CNVs associated with mental disorders in 5364 individuals. The Brazilian high-risk cohort for mental disorders or Brazilian High-Risk Cohort (BHRC) comprises approximately 2500 families (1000 randomly selected and 1500 at risk for mental disorders) and is a longitudinal study focused on the brain development and mental health of adolescents with three collections already completed: baseline in 2010 with children aged 6 to 12 years; first follow-up in 2014 with individuals between 9 and 17 years old; and second follow-up in 2019 with adolescents between 14 and 23 years old. The sample of 2190 children/adolescents and 3174 parents was genotyped with Illumina's Global Screening Array. We will use the plink tool for quality control of genomic data and the PennCNV tool to generate CNV data. Then, we will associate the presence of deletions and duplications with the psychiatric diagnosis available for the 3 phases of the study. In addition, with almost 900 trios and 1100 duos available, we will be able to infer whether these CNVs are inherited or de novo CNVs. With this study, we intend to identify already known pathogenic CNVs related to mental disorders, in addition to training a student, still in HF, with advanced bioinformatics techniques. Finally, this data will contribute to other ongoing studies in the cohort that jointly evaluate data on neuroimaging, genetic risk, environmental risk and others. (AU)