Genome-Wide Association Study in German Patients With Attention Deficit/Hyperactivity Disorder

被引：74

作者：

Hinney, Anke ^{[1
]}

Scherag, Andre ^{[2
]}

Jarick, Ivonne ^{[3
]}

Albayrak, Oezguer ^{[1
]}

Puetter, Carolin ^{[2
]}

Pechlivanis, Sonali ^{[2
]}

Dauvermann, Maria R. ^{[1
,4
]}

Beck, Sebastian ^{[1
]}

Weber, Heike ^{[5
]}

Scherag, Susann ^{[1
]}

Nguyen, Trang T. ^{[3
]}

Volckmar, Anna-Lena

Knoll, Nadja

Faraone, Stephen V. ^{[6
]}

Neale, Benjamin M. ^{[7
,8
]}

Franke, Barbara ^{[9
,10
]}

Cichon, Sven ^{[11
,12
,13
]}

Hoffmann, Per ^{[12
,13
]}

Noethen, Markus M. ^{[12
,13
]}

Schreiber, Stefan ^{[14
]}

Joeckel, Karl-Heinz ^{[2
]}

Wichmann, H. -Erich ^{[15
]}

Freitag, Christine ^{[16
]}

Lempp, Thomas ^{[16
]}

Meyer, Jobst ^{[17
]}

Gilsbach, Susanne ^{[18
]}

Herpertz-Dahlmann, Beate ^{[18
]}

Sinzig, Judith ^{[19
,20
]}

Lehmkuhl, Gerd ^{[19
]}

Renner, Tobias J. ^{[5
]}

Warnke, Andreas ^{[5
]}

Romanos, Marcel ^{[21
]}

Lesch, Klaus-Peter ^{[22
]}

Reif, Andreas ^{[22
]}

Schimmelmann, Benno G. ^{[1
,4
]}

Hebebrand, Johannes ^{[1
]}

机构：

[1] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany

[2] Univ Duisburg Essen, IMIBE, D-45147 Essen, Germany

[3] Univ Marburg, Inst Med Biometrie & Epidemiol, Marburg, Germany

[4] Univ Bern, Univ Hosp Child & Adolescent Psychiat, Bern, Switzerland

[5] Univ Wurzburg, Dept Child & Adolescent Psychiat, Wurzburg, Germany

[6] SUNY Upstate Med Univ, Syracuse, NY USA

[7] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[8] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA

[9] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[10] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands

[11] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany

[12] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany

[13] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany

[14] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany

[15] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany

[16] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Frankfurt, Germany

[17] Univ Trier, Inst Psychobiol, Dept Neurobehav Genet, Trier, Germany

[18] Rhein Westfal TH Aachen, Univ Clin, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany

[19] Univ Cologne, Dept Child & Adolescent Psychiat, Cologne, Germany

[20] LVR Clin Bonn, Dept Child & Adolescent Psychiat & Psychotherapy, Bonn, Germany

[21] Univ Hosp Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany

[22] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2011年 / 156B卷 / 08期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

psychiatric; children; early onset; homogeneous; DEFICIT HYPERACTIVITY DISORDER; MOLECULAR-GENETICS; COMMON VARIANTS; ADHD; GENES; METAANALYSIS; SCAN; RISK; LOCI; SUPPORTS;

D O I：

10.1002/ajmg.b.31246

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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 x 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. (C) 2011 Wiley Periodicals, Inc.

引用

页码：888 / 897

页数：10

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