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Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations

Lasky-Su, Jessica and Neale, Benjamin M. and Franke, Barbara and Anney, Richard J. L. and Zhou, Kaixin and Maller, Julian B. and Vasquez, Alejandro Arias and Chen, Wai and Asherson, Philip and Buitelaar, Jan and Banaschewski, Tobias and Ebstein, Richard and Gill, Michael and Miranda, Ana and Mulas, Fernando and Oades, Robert D. and Roeyers, Herbert and Rothenberger, Aribert and Sergeant, Joseph and Sonuga-Barke, Edmund and Steinhausen, Hans Christoph and Taylor, Eric and Daly, Mark and Laird, Nan and Lange, Christoph and Faraone, Stephen V.. (2008) Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol. 147B, H. 8. pp. 1345-1354.

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Official URL: http://edoc.unibas.ch/dok/A5250668

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Abstract

Attention deficit hyperactivity disorder (ADHD) is a complex condition with environmental and genetic etiologies. Up to this point, research has identified genetic associations with candidate genes from known biological pathways. In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. We generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. CDH13 has been implicated previously in substance use disorders. We also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association P-values with a magnitude less than 10(-5), are discussed in this manuscript. Seventeen of these candidate genes had association P-values lower then 0.01: SLC6A1, SLC9A9, HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test P-values lower than 0.01 and multiple association P-values at a magnitude of 10(-5) in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirm the proposed genetic variants for ADHD.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie > Ehemalige Einheiten Psychologie > Clinical Child and Adolescent Psychology (Schneider)
UniBasel Contributors:Steinhausen, Hans-Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley-Liss
ISSN:1552-4841
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:37

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