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De Novo, Rare Inherited Copy Number Variations Tied to ADHD
Updated: Aug 11th 2011
THURSDAY, Aug. 11 (HealthDay News) -- De novo and rare inherited copy number variations (CNVs) are associated with attention deficit hyperactivity disorder (ADHD), and include genes previously implicated by rare CNVs in other neurodevelopmental conditions including autism spectrum disorder (ASD), according to a study published in the Aug. 10 issue of Science Translational Medicine.
Anath Christopher Lionel, from the Hospital for Sick Children in Toronto, and colleagues identified de novo and rare CNVs in unrelated patients with ADHD using million-feature genotyping microarrays. A total of 248 unrelated patients with ADHD and 2,357 control individuals were included in the study. The same microarrays were performed for 349 unrelated patients with ASD to identify the CNVs overlapping between ADHA and ASD.
The investigators identified de novo CNVs in three out of 173 patients with ADHD for whom DNA from both parents were available, and they affected the brain-expressed genes DCLK2, SORCS1, SORCS3, and MACROD2. Rare inherited CNVs, which were absent in the controls, were found in 19 patients with ADHD. These genes either overlapped with previously implicated ADHD loci or identified new candidate susceptibility genes. The de novo and rare inherited CNVs included genes previously implicated by rare CNVs in other neurodevelopmental conditions including ASD. ADHD and ASD shared numerous candidate genes, but the deletion of neuronal ASTN2 and ASTN2 intronic TRIM32 genes confirmed the strongest association.
"Our results provide support for a role for rare CNVs in ADHD risk and reinforce evidence for the existence of common underlying susceptibility genes for ADHD, ASD, and other neuropsychiatric disorders," the authors write.
Two authors disclosed financial ties to the pharmaceutical industry and Genome Canada, which funded the study. Two authors have filed a patent on the use of ASTN2 and other CNVs in the diagnosis of ADHD based on the data from this study.
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