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

共 52 条

[1] Molecular genetics of attention-deficit/hyperactivity disorder: an overview [J].

Banaschewski, Tobias ;

Becker, Katja ;

Scherag, Susann ;

Franke, Barbara ;

Coghill, David .

EUROPEAN CHILD & ADOLESCENT PSYCHIATRY, 2010, 19 (03) :237-257

[2] DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores: A Sampling Strategy For QTL Linkage [J].

Chen, Wai ;

Zhou, Kaixin ;

Sham, Pak ;

Franke, Barbara ;

Kuntsi, Jonna ;

Campbell, Desmond ;

Fleischman, Karin ;

Knight, Jo ;

Andreou, Penny ;

Arnold, Renee ;

Altink, Marieke ;

Boer, Frits ;

Boholst, Mary Jane ;

Buschgens, Catheljjne ;

Butler, Louise ;

Christiansen, Hanna ;

Fliers, Ellen ;

Howe-Forbes, Raoul ;

Gabriels, Isabel ;

Heise, Alexander ;

Korn-Lubetzki, Isabelle ;

Marco, Rafaela ;

Medad, She'era ;

Minderaa, Ruud ;

Mueller, Ueli C. ;

Mulligan, Aisling ;

Psychogiou, Lamprini ;

Rommelse, Nanda ;

Sethna, Vaheshta ;

Uebel, Henrik ;

McGuffin, Peter ;

Plomin, Robert ;

Banaschewski, Tobias ;

Buitelaar, Jan ;

Ebstein, Richard ;

Eisenberg, Jacques ;

Gill, Michael ;

Manor, Iris ;

Miranda, Ana ;

Mulas, Fernando ;

Oades, Robert D. ;

Roeyers, Herbert ;

Rothenberger, Aribert ;

Sergeant, Joseph ;

Sonuga-Barke, Edmund J. S. ;

Steinhausen, Hans-Christoph ;

Taylor, Eric ;

Thompson, Margaret ;

Faraone, Stephen V. ;

Asherson, Philip .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2008, 147B (08) :1450-1460

[3] Genome-wide Association Study Identifies Genetic Variation in Neurocan as a Susceptibility Factor for Bipolar Disorder [J].

Cichon, Sven ;

Muehleisen, Thomas W. ;

Degenhardt, Franziska A. ;

Mattheisen, Manuel ;

Miro, Xavier ;

Strohmaier, Jana ;

Steffens, Michael ;

Meesters, Christian ;

Herms, Stefan ;

Weingarten, Moritz ;

Priebe, Lutz ;

Haenisch, Britta ;

Aexander, Michael ;

Vollmer, Jennifer ;

Breuer, Rene ;

Schmael, Christine ;

Tessmann, Peter ;

Moebus, Susanne ;

Wichmann, H. -Erich ;

Schreiber, Stefan ;

Mueller-Myhsok, Bertram ;

Lucae, Susanne ;

Jamain, Stephane ;

Leboyer, Marion ;

Bellivier, Frank ;

Etain, Bruno ;

Henry, Chantal ;

Kahn, Jean-Pierre ;

Heath, Simon ;

Hamshere, Marian ;

O'Donovan, Michael C. ;

Owen, Michael J. ;

Craddock, Nick ;

Schwarz, Markus ;

Vedder, Helmut ;

Kammerer-Ciernioch, Jutta ;

Reif, Andreas ;

Sasse, Johanna ;

Bauer, Michael ;

Hautzinger, Martin ;

Wright, Adam ;

Mitchell, Philip B. ;

Schofield, Peter R. ;

Montgomery, Grant W. ;

Medland, Sarah E. ;

Gordon, Scott D. ;

Martin, Nicholas G. ;

Gustafsson, Omar ;

Andreassen, Ole ;

Djurovic, Srdjan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 88 (03) :372-381

[4] A framework for interpreting genome-wide association studies of psychiatric disorders The Psychiatric GWAS Consortium Steering Committee [J].

Cichon, Sven ;

Craddock, Nick ;

Daly, Mark ;

Faraone, Stephen V. ;

Gejman, Pablo V. ;

Kelsoe, John ;

Lehner, Thomas ;

Levinson, Douglas F. ;

Moran, Audra ;

Sklar, Pamela ;

Sullivan, Patrick F. .

MOLECULAR PSYCHIATRY, 2009, 14 (01) :10-17

[5] Genomic control for association studies [J].

Devlin, B ;

Roeder, K .

BIOMETRICS, 1999, 55 (04) :997-1004

[6] Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes [J].

Elia, J. ;

Gai, X. ;

Xie, H. M. ;

Perin, J. C. ;

Geiger, E. ;

Glessner, J. T. ;

D'arcy, M. ;

deBerardinis, R. ;

Frackelton, E. ;

Kim, C. ;

Lantieri, F. ;

Muganga, B. M. ;

Wang, L. ;

Takeda, T. ;

Rappaport, E. F. ;

Grant, S. F. A. ;

Berrettini, W. ;

Devoto, M. ;

Shaikh, T. H. ;

Hakonarson, H. ;

White, P. S. .

MOLECULAR PSYCHIATRY, 2010, 15 (06) :637-646

[7] Molecular Genetics of Attention Deficit Hyperactivity Disorder [J].

Faraone, Stephen V. ;

Mick, Eric .

PSYCHIATRIC CLINICS OF NORTH AMERICA, 2010, 33 (01) :159-+

[8] Molecular genetics of attention-deficit/hyperactivity disorder [J].

Faraone, SV ;

Perlis, RH ;

Doyle, AE ;

Smoller, JW ;

Goralnick, JJ ;

Holmgren, MA ;

Sklar, P .

BIOLOGICAL PSYCHIATRY, 2005, 57 (11) :1313-1323

[9] Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder [J].

Ferreira, Manuel A. R. ;

O'Donovan, Michael C. ;

Meng, Yan A. ;

Jones, Ian R. ;

Ruderfer, Douglas M. ;

Jones, Lisa ;

Fan, Jinbo ;

Kirov, George ;

Perlis, Roy H. ;

Green, Elaine K. ;

Smoller, Jordan W. ;

Grozeva, Detelina ;

Stone, Jennifer ;

Nikolov, Ivan ;

Chambert, Kimberly ;

Hamshere, Marian L. ;

Nimgaonkar, Vishwajit L. ;

Moskvina, Valentina ;

Thase, Michael E. ;

Caesar, Sian ;

Sachs, Gary S. ;

Franklin, Jennifer ;

Gordon-Smith, Katherine ;

Ardlie, Kristin G. ;

Gabriel, Stacey B. ;

Fraser, Christine ;

Blumenstiel, Brendan ;

Defelice, Matthew ;

Breen, Gerome ;

Gill, Michael ;

Morris, Derek W. ;

Elkin, Amanda ;

Muir, Walter J. ;

McGhee, Kevin A. ;

Williamson, Richard ;

MacIntyre, Donald J. ;

MacLean, Alan W. ;

Clair, David St ;

Robinson, Michelle ;

Van Beck, Margaret ;

Pereira, Ana C. P. ;

Kandaswamy, Radhika ;

McQuillin, Andrew ;

Collier, David A. ;

Bass, Nicholas J. ;

Young, Allan H. ;

Lawrence, Jacob ;

Ferrier, I. Nicol ;

Anjorin, Adebayo ;

Farmer, Anne .

NATURE GENETICS, 2008, 40 (09) :1056-1058

[10] Multicenter Analysis of the SLC6A3/DAT1 VNTR Haplotype in Persistent ADHD Suggests Differential Involvement of the Gene in Childhood and Persistent ADHD [J].

Franke, Barbara ;

Vasquez, Alejandro Arias ;

Johansson, Stefan ;

Hoogman, Martine ;

Romanos, Jasmin ;

Boreatti-Huemmer, Andrea ;

Heine, Monika ;

Jacob, Christian P. ;

Lesch, Klaus-Peter ;

Casas, Miguel ;

Ribases, Marta ;

Bosch, Rosa ;

Sanchez-Mora, Cristina ;

Gomez-Barros, Nuria ;

Fernandez-Castillo, Noelia ;

Bayes, Monica ;

Halmoy, Anne ;

Halleland, Helene ;

Landaas, Elisabeth T. ;

Fasmer, Ole B. ;

Knappskog, Per M. ;

Heister, Angelien J. G. A. M. ;

Kiemeney, Lambertus A. ;

Kooij, J. J. Sandra ;

Boonstra, A. Marije ;

Kan, Cees C. ;

Asherson, Philip ;

Faraone, Stephen V. ;

Buitelaar, Jan K. ;

Haavik, Jan ;

Cormand, Bru ;

Antoni Ramos-Quiroga, Josep ;

Reif, Andreas .

NEUROPSYCHOPHARMACOLOGY, 2010, 35 (03) :656-664

← 1 2 3 4 5 6 →