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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<jats:italic>de novo<\/jats:italic>SNVs tend not to have<jats:italic>de novo<\/jats:italic>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 \u201cin silico\u201d 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.<\/jats:p>","DOI":"10.1038\/srep22851","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T10:20:39Z","timestamp":1457346039000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit\/Hyperactivity Disorder"],"prefix":"10.1038","volume":"6","author":[{"given":"Leandro","family":"de Ara\u00fajo Lima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana 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The error has not been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ary Gadelha, Pedro Mario Pan, and Tais Silveira Moriyama have received continuous medical education support from Astra Zeneca, Eli-Lilly and Janssen-Cilag. Guilherme Vanoni Polanczyk has aided as a speaker and\/or consultant to Eli-Lilly, Novartis, and Shire Pharmaceuticals, developed educational material to Janssen-Cilag, and receives unrestricted research support from Novartis. Maria Concei\u00e7\u00e3o do Ros\u00e1rio has worked for the last five years as a speaker for the companies Novartis and Shire. Rodrigo A. Bressan was on the speakers\u2019 bureau and\/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis, Lundbek and Roche in the last three years. Luis Augusto Rohde was on the speakers\u2019 bureau and\/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis and Shire in the last three years. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LAR received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Abbott; Eli-Lilly; Janssen-Cilag; Novartis; Shire. All other authors declare no potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22851"}}