An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in attention-deficit/hyperactivity disorder

• Autor(a) principal: Lima, Leandro de Araújo
• Data de Publicação: 2016
• Outros Autores: Feio-dos-Santos, Ana Cecília, Belangero, Síntia Iole Nogueira, Gadelha, Ary, Bressan, Rodrigo Affonseca, Salum Junior, Giovanni Abrahão, Pan, Pedro Mario, Moriyama, Taís Silveira, Graeff-Martins, Ana Soledade, Tamanaha, Márcia, Alvarenga, Pedro Gomes de, Krieger, Fernanda Valle, Bilyk, Bacy Fleitlich, Jackowski, Andrea Parolin, Brietzke, Elisa Macedo, Sato, João Ricardo, Polanczyk, Guilherme Vanoni, Mari, Jair de Jesus, Manfro, Gisele Gus, Rosário, Maria Conceição do, Miguel, Eurípedes Constantino, Puga, Renato David, Tahira, Ana Carolina, Souza, Viviane Neri, Chile, Thais, Gouveia, Gisele Rodrigues, Simões, Sérgio Nery, Chang, Xiao, Pellegrino, Renata, Tian, Lifeng, Glessner, Joseph T., Hashimoto, Ronaldo Fumio, Rohde, Luis Augusto Paim, Sleiman, Patrick M.A., Hakonarson, Hakon, Brentani, Helena Paula
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/149756
• topic: Transtorno do déficit de atenção com hiperatividade; Polimorfismo de nucleotídeo único

Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/ Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS metaanalysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two “in silico” protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.