Identificação de copy number variations (CNVs) em uma coorte brasileira de alto risco para transtornos mentais
Arquivos
Data
2023-12-11
Autores
Antonieto, Júlia Arendt 
Orientadores
Santoro, Marcos Leite
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Os transtornos mentais têm sido negligenciados no sistema de saúde pública, especialmente em países de baixa ou média renda, apesar de ser uma das causas de anos de vida perdidos devido à incapacidade. Eles possuem alta correlação genética e são altamente herdáveis. Variantes genéticas raras com alto tamanho de efeito, como variações no número de cópias (CNVs), têm um impacto conhecido no desenvolvimento destes transtornos. Neste estudo, objetivamos caracterizar as CNVs presentes em uma amostra brasileira e seu impacto em fenótipos psiquiátricos e dados de desempenho cognitivo e escolar. Buscamos também identificar em nossa amostra, CNVs previamente associadas a transtornos mentais. 2.190 adolescentes e jovens adultos e 3.174 pais (897 trios) da coorte brasileira de alto risco para transtornos mentais (BHRCS) foram genotipados com Global-Screening-Array e as CNVs foram identificadas usando o software PennCNV. Para caracterização da amostra, a frequência e a herança de CNVs foram investigadas. Em trios, pode-se concluir que 61,92% das CNVs identificadas são herdadas. Com significância estatística, foi observado que quanto maior a soma do tamanho das CNVs por indivíduo (CNV burden), pior a habilidade de escrita na BHRCS. CNVs previamente associadas a transtornos mentais foram selecionadas e identificadas na amostra. A deleção em 15q11.2, por exemplo, foi significativa para mães com esquizofrenia (p = 0,028 OR = 10,020). Outras regiões foram encontradas com maior frequência no grupo com diagnóstico psiquiátrico do que nos controles, mas sem significância estatística. Em conjunto, os nossos resultados podem ajudar a compreender a etiologia e transição para os transtornos ao longo do tempo. Este é um dos maiores estudos de CNV em uma amostra brasileira e levou a uma melhor compreensão da genética e do risco de transtornos mentais na coorte.
Mental disorders have been neglected in the public health system, especially in low- or middle-income countries, despite being one of the leading causes of years of life lost due to disability. They have a high genetic correlation and are highly heritable. Rare genetic variants with a large effect size, such as copy number variations (CNVs), have a known impact on the development of these disorders. In this study, our aim was to characterize the CNVs present in a Brazilian sample and their impact on psychiatric phenotypes, cognitive performance, and school accomplishment. We also sought to identify CNVs previously associated with mental disorders in our sample. A total of 2,190 adolescents and young adults, along with 3,174 parents (897 trios) from the Brazilian High-Risk Cohort for Mental Disorders (BHRCS), were genotyped using the Global-Screening-Array, and CNVs were identified using PennCNV software. For sample characterization, the frequency and inheritance of CNVs were investigated. In trios, it was concluded that 61.92% of the identified CNVs are inherited. With statistical significance, it was observed that the higher the sum of CNV sizes per individual (CNV burden), the worse the writing ability in the BHRCS. CNVs previously associated with mental disorders were selected and identified in the sample. Deletion in 15q11.2, for example, was significant for mothers with schizophrenia (p = 0.028, OR = 10.020). Other regions were found more frequently in the psychiatric diagnosis group than in controls, but without statistical significance. Overall, our results may contribute to understanding the etiology and transition to disorders over time. This is one of the largest CNV studies in a Brazilian sample and has led to a better understanding of the genetics and risk of mental disorders in the cohort.
Mental disorders have been neglected in the public health system, especially in low- or middle-income countries, despite being one of the leading causes of years of life lost due to disability. They have a high genetic correlation and are highly heritable. Rare genetic variants with a large effect size, such as copy number variations (CNVs), have a known impact on the development of these disorders. In this study, our aim was to characterize the CNVs present in a Brazilian sample and their impact on psychiatric phenotypes, cognitive performance, and school accomplishment. We also sought to identify CNVs previously associated with mental disorders in our sample. A total of 2,190 adolescents and young adults, along with 3,174 parents (897 trios) from the Brazilian High-Risk Cohort for Mental Disorders (BHRCS), were genotyped using the Global-Screening-Array, and CNVs were identified using PennCNV software. For sample characterization, the frequency and inheritance of CNVs were investigated. In trios, it was concluded that 61.92% of the identified CNVs are inherited. With statistical significance, it was observed that the higher the sum of CNV sizes per individual (CNV burden), the worse the writing ability in the BHRCS. CNVs previously associated with mental disorders were selected and identified in the sample. Deletion in 15q11.2, for example, was significant for mothers with schizophrenia (p = 0.028, OR = 10.020). Other regions were found more frequently in the psychiatric diagnosis group than in controls, but without statistical significance. Overall, our results may contribute to understanding the etiology and transition to disorders over time. This is one of the largest CNV studies in a Brazilian sample and has led to a better understanding of the genetics and risk of mental disorders in the cohort.
Descrição
Citação
Antonieto, Júlia Arendt. Identificação de copy number variations (CNVs) em uma coorte brasileira de alto risco para transtornos mentais. 2023. Trabalho de Conclusão de Curso (Graduação em Biomedicina) - Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, 2023.