An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder

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Lima, Leandro de Araujo ^{[1, 2]} ; Feio-dos-Santos, Ana Cecilia ^[3] ; Belangero, Sintia Iole ^{[4, 5]} ; Gadelha, Ary ^{[4, 5]} ; Bressan, Rodrigo Affonseca ^{[4, 5]} ; Salum, Giovanni Abrahao ^{[5, 6]} ; Pan, Pedro Mario ^{[4, 5]} ; Moriyama, Tais Silveira ^{[4, 3, 5]} ; Graeff-Martins, Ana Soledade ^{[3, 5]} ; Tamanaha, Ana Carina ^{[4, 5]} ; Alvarenga, Pedro ^{[3, 5]} ; Krieger, Fernanda Valle ^{[3, 5]} ; Fleitlich-Bilyk, Bacy ^{[3, 5]} ; Jackowski, Andrea Parolin ^{[4, 5]} ; Brietzke, Elisa ^{[4, 5]} ; Sato, Joao Ricardo ^{[7, 5]} ; Polanczyk, Guilherme Vanoni ^{[3, 5]} ; Mari, Jair de Jesus ^{[4, 5]} ; Manfro, Gisele Gus ^{[5, 6]} ; do Rosario, Maria Conceicao ^{[4, 5]} ; Miguel, Euripedes Constantino ^{[3, 5]} ; Puga, Renato David ^[8] ; Tahira, Ana Carolina ^[3] ; Souza, Viviane Neri ^[3] ; Chile, Thais ^[3] ; Gouveia, Gisele Rodrigues ^[3] ; Simoes, Sergio Nery ^{[9, 2]} ; Chang, Xiao ^[1] ; Pellegrino, Renata ^[1] ; Tian, Lifeng ^[1] ; Glessner, Joseph T. ^[1] ; Hashimoto, Ronaldo Fumio ^{[10, 2]} ; Rohde, Luis Augusto ^{[3, 5, 6]} ; Sleiman, Patrick M. A. ^{[1, 11]} ; Hakonarson, Hakon ^{[1, 11]} ; Brentani, Helena ^{[3, 5, 2]}

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^[1] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 - USA

^[2] Univ Sao Paulo, Interinst Grad Program Bioinformat, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept & Inst Psychiat, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, SP - Brazil

^[5] Natl Inst Dev Psychiat Children & Adolescents INC, Sao Paulo, SP - Brazil

^[6] Univ Fed Rio Grande do Sul, Dept Psychiat, Hosp Clin Porto Alegre, Porto Alegre, RS - Brazil

^[7] Univ Fed ABC, Ctr Math Computat & Cognit, Santo Andre - Brazil

^[8] Hosp Israelita Albert Einstein, Clin Res, Sao Paulo, SP - Brazil

^[9] Fed Inst Espirito Santo, Serra, ES - Brazil

^[10] Univ Sao Paulo, Math & Stat Inst, Sao Paulo, SP - Brazil

^[11] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 - USA

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 6, MAR 7 2016.
• Citações Web of Science: 2

Resumo

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 meta-analysis 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. (AU)

• Processo FAPESP: 08/57896-8 - O Instituto Nacional da Psiquiatria do Desenvolvimento: uma nova abordagem para a psiquiatria tendo como foco as nossas crianças e o seu futuro
• Beneficiário: Eurípedes Constantino Miguel Filho
• Modalidade de apoio: Auxílio à Pesquisa - Temático