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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Date
2016Author
Lima, Leandro de Araujo
Feio-dos-Santos, Ana Cecilia
Belangero, Sintia Iole [UNIFESP]
Gadelha, Ary [UNIFESP]
Bressan, Rodrigo Affonseca [UNIFESP]
Salum, Giovanni Abrahao
Pan, Pedro Mario [UNIFESP]
Moriyama, Tais Silveira [UNIFESP]
Graeff-Martins, Ana Soledade
Tamanaha, Ana Carina [UNIFESP]
Alvarenga, Pedro
Krieger, Fernanda Valle
Fleitlich-Bilyk, Bacy
Jackowski, Andrea Parolin [UNIFESP]
Brietzke, Elisa [UNIFESP]
Sato, Joao Ricardo
Polanczyk, Guilherme Vanoni
Mari, Jair de Jesus [UNIFESP]
Manfro, Gisele Gus [UNIFESP]
do Rosario, Maria Conceicao [UNIFESP]
Miguel, Euripedes Constantino
Puga, Renato David
Tahira, Ana Carolina
Souza, Viviane Neri
Chile, Thais
Gouveia, Gisele Rodrigues
Simoes, Sergio Nery
Chang, Xiao
Pellegrino, Renata
Tian, Lifeng
Glessner, Joseph T.
Hashimoto, Ronaldo Fumio
Rohde, Luis Augusto [UNIFESP]
Sleiman, Patrick M. A.
Hakonarson, Hakon
Brentani, Helena
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Show full item recordAbstract
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.
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