Genome-wide association study in German patients with attention deficit/hyperactivity disorder.

2.50
Hdl Handle:
http://hdl.handle.net/2336/225677
Title:
Genome-wide association study in German patients with attention deficit/hyperactivity disorder.
Authors:
Hinney, Anke; Scherag, André; Jarick, Ivonne; Albayrak, Özgür; Pütter, Carolin; Pechlivanis, Sonali; Dauvermann, Maria R; Beck, Sebastian; Weber, Heike; Scherag, Susann; Nguyen, Trang T; Volckmar, Anna-Lena; Knoll, Nadja; Faraone, Stephen V; Neale, Benjamin M; Franke, Barbara; Cichon, Sven; Hoffmann, Per; Nöthen, Markus M; Schreiber, Stefan; Jöckel, Karl-Heinz; Wichmann, H-Erich; Freitag, Christine; Lempp, Thomas; Meyer, Jobst; Gilsbach, Susanne; Herpertz-Dahlmann, Beate; Sinzig, Judith; Lehmkuhl, Gerd; Renner, Tobias J; Warnke, Andreas; Romanos, Marcel; Lesch, Klaus-Peter; Reif, Andreas; Schimmelmann, Benno G; Hebebrand, Johannes; Palmason, H
Citation:
Am. J. Med. Genet. B Neuropsychiatr. Genet. 2011, 156B(8):888-97
Issue Date:
Dec-2011
Abstract:
The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links:
http://dx.doi.org/10.1002/ajmg.b.31246
Rights:
Archived with thanks to American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

Full metadata record

DC FieldValue Language
dc.contributor.authorHinney, Ankeen_GB
dc.contributor.authorScherag, Andréen_GB
dc.contributor.authorJarick, Ivonneen_GB
dc.contributor.authorAlbayrak, Özgüren_GB
dc.contributor.authorPütter, Carolinen_GB
dc.contributor.authorPechlivanis, Sonalien_GB
dc.contributor.authorDauvermann, Maria Ren_GB
dc.contributor.authorBeck, Sebastianen_GB
dc.contributor.authorWeber, Heikeen_GB
dc.contributor.authorScherag, Susannen_GB
dc.contributor.authorNguyen, Trang Ten_GB
dc.contributor.authorVolckmar, Anna-Lenaen_GB
dc.contributor.authorKnoll, Nadjaen_GB
dc.contributor.authorFaraone, Stephen Ven_GB
dc.contributor.authorNeale, Benjamin Men_GB
dc.contributor.authorFranke, Barbaraen_GB
dc.contributor.authorCichon, Svenen_GB
dc.contributor.authorHoffmann, Peren_GB
dc.contributor.authorNöthen, Markus Men_GB
dc.contributor.authorSchreiber, Stefanen_GB
dc.contributor.authorJöckel, Karl-Heinzen_GB
dc.contributor.authorWichmann, H-Erichen_GB
dc.contributor.authorFreitag, Christineen_GB
dc.contributor.authorLempp, Thomasen_GB
dc.contributor.authorMeyer, Jobsten_GB
dc.contributor.authorGilsbach, Susanneen_GB
dc.contributor.authorHerpertz-Dahlmann, Beateen_GB
dc.contributor.authorSinzig, Judithen_GB
dc.contributor.authorLehmkuhl, Gerden_GB
dc.contributor.authorRenner, Tobias Jen_GB
dc.contributor.authorWarnke, Andreasen_GB
dc.contributor.authorRomanos, Marcelen_GB
dc.contributor.authorLesch, Klaus-Peteren_GB
dc.contributor.authorReif, Andreasen_GB
dc.contributor.authorSchimmelmann, Benno Gen_GB
dc.contributor.authorHebebrand, Johannesen_GB
dc.contributor.authorPalmason, Hen_GB
dc.date.accessioned2012-05-24T11:23:34Z-
dc.date.available2012-05-24T11:23:34Z-
dc.date.issued2011-12-
dc.date.submitted2012-05-24-
dc.identifier.citationAm. J. Med. Genet. B Neuropsychiatr. Genet. 2011, 156B(8):888-97en_GB
dc.identifier.issn1552-485X-
dc.identifier.pmid22012869-
dc.identifier.doi10.1002/ajmg.b.31246-
dc.identifier.urihttp://hdl.handle.net/2336/225677-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractThe heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.en_GB
dc.description.sponsorshipGerman Research Association (DFG) He1446/9-1 KFO 125 SFB 581 GRK 1156 ME 1923/5-1 ME 1923/5-3 GRK 1389 SCHA 542/10-3 Bundesministerium fur Bildung und Forschung BMBF 01GV0605 Medical Faculty, RWTH Aachen, Germany EK 119/05 US National of Institute of Health R13MH059126 R01MH62873 R01MH081803 K23MH066275 University of Pennsylvania CTR UL1-RR-024134 Children's Hospital of Philadelphia Affymetrix Power Award NHMRC (Australia) Sidney Sax Public Health Fellowship 443036 UMC Utrecht Genvlag Grant Radboud University Nijmegen Medical Centreen_GB
dc.language.isoenen
dc.publisherWiley-Lissen_GB
dc.relation.urlhttp://dx.doi.org/10.1002/ajmg.b.31246en_GB
dc.rightsArchived with thanks to American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Geneticsen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAttention Deficit Disorder with Hyperactivityen_GB
dc.subject.meshChilden_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGenetic Markersen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshGermanyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshReceptors, Metabotropic Glutamateen_GB
dc.titleGenome-wide association study in German patients with attention deficit/hyperactivity disorder.en
dc.typeArticleen
dc.contributor.departmentDepartment of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany. anke.hinney@uni-due.deen_GB
dc.identifier.journalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Geneticsen_GB

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