Genome-wide association scan of quantitative traits for Attention Deficit Hyperactivity Disorder identifies novel associations and confirms candidate gene associations
Lasky-Su, Jessica, Neale, Benjamin M., Franke, Barbara, Anney, Richard J.L., Zhou, Kaixin, Maller, Julian B., Vasquez, Alejandro Arias, Chen, Wai, Asherson, Philip, Buitelaar, Jan K, Banaschewski, Tobias, Ebstein, Richard, Gill, Michael, Miranda, Ana, Mulas, Fernando, Oades, Robert D., Roeyers, Herbert, Rothenberger, Aribert, Sergeant, Joseph A, Sonuga-Barke, Edmund J.S., Steinhausen, Hans-Christoph, Taylor, Eric A, Daly, Mark, Laird, Nan, Lange, Christoph, Faraone, Stephen V.
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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 genomewide
association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113
and rs552655 that met criteria for genome-wide 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.
Lesezeichen:
Dokumententyp:
Wissenschaftliche Texte » Artikel, Aufsatz
Fakultät / Institut:
Medizinische Fakultät / Universitätsklinikum » Rheinische Kliniken Essen » Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters
Dewey Dezimal-Klassifikation:
600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit » 610 Medizin und Gesundheit
Stichwörter:
ADHD, genome-wide association, family-based association, candidate gene, CDH13
Sprache:
Englisch
Kollektion / Status:
E-Publikationen / Dokument veröffentlicht
Dateien geändert am:
15.09.2011
Medientyp:
Text
Rechtliche Vermerke:
pre-publication text
Quelle:
Final version in: American journal of medical genetics, Part B, Neuropsychiatric genetics, Vol. 147 (2008) ; no. 8, p. 1345-1354 ISSN: 0148-7299, 1552-4841 DOI 10.1002/ajmg.b.30867
