Genome‐wide association study in German patients with attention deficit/hyperactivity disorder
Identifieur interne : 000987 ( Main/Exploration ); précédent : 000986; suivant : 000988Genome‐wide association study in German patients with attention deficit/hyperactivity disorder
Auteurs : Anke Hinney [Allemagne] ; André Scherag [Allemagne] ; Ivonne Jarick [Allemagne] ; Özgür Albayrak [Allemagne] ; Carolin Pütter [Allemagne] ; Sonali Pechlivanis [Allemagne] ; Maria R. Dauvermann [Allemagne, Suisse] ; Sebastian Beck [Allemagne] ; Heike Weber [Allemagne] ; Susann Scherag [Allemagne] ; Trang T. Nguyen [Allemagne] ; Anna-Lena Volckmar [Allemagne] ; Nadja Knoll [Allemagne] ; Stephen V. Faraone [États-Unis] ; Benjamin M. Neale [États-Unis] ; Barbara Franke [Pays-Bas] ; Sven Cichon [Allemagne] ; Per Hoffmann [Allemagne] ; Markus M. Nöthen [Allemagne] ; Stefan Schreiber [Allemagne] ; Karl-Heinz Jöckel [Allemagne] ; H. Rich Wichmann [Allemagne] ; Christine Freitag [Allemagne] ; Thomas Lempp [Allemagne] ; Jobst Meyer [Allemagne] ; Susanne Gilsbach [Allemagne] ; Beate Herpertz-Dahlmann [Allemagne] ; Judith Sinzig [Allemagne] ; Gerd Lehmkuhl [Allemagne] ; Tobias J. Renner [Allemagne] ; Andreas Warnke [Allemagne] ; Marcel Romanos [Allemagne] ; Klaus-Peter Lesch [Allemagne] ; Andreas Reif [Allemagne] ; Benno G. Schimmelmann [Allemagne, Suisse] ; Johannes Hebebrand [Allemagne]Source :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2011-12.
Descripteurs français
- Pascal (Inist)
- Wicri :
- geographic : Allemagne.
- topic : Association, Enfant, Homme.
English descriptors
- KwdEn :
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. © 2011 Wiley Periodicals, Inc.
Url:
DOI: 10.1002/ajmg.b.31246
Affiliations:
- Allemagne, Pays-Bas, Suisse, États-Unis
- Bavière, Canton de Berne, District de Cologne, District de Darmstadt, District de Giessen, District de Haute-Bavière, Gueldre, Hesse (Land), Massachusetts, Rhénanie-Palatinat, Rhénanie-du-Nord-Westphalie, Schleswig-Holstein, État de New York
- Aix-la-Chapelle, Berne, Bonn, Francfort-sur-le-Main, Kiel, Marbourg, Munich, Nimègue, Trèves (Allemagne)
- Université de Trèves
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Le document en format XML
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<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Genomics, Life & Brain Center, University of Bonn, Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
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<settlement type="city">Kiel</settlement>
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<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen</wicri:regionArea>
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<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
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<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
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<wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main</wicri:regionArea>
<placeName><region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Darmstadt</region>
<settlement type="city">Francfort-sur-le-Main</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lempp, Thomas" sort="Lempp, Thomas" uniqKey="Lempp T" first="Thomas" last="Lempp">Thomas Lempp</name>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main</wicri:regionArea>
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<region type="district" nuts="2">District de Darmstadt</region>
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<affiliation wicri:level="4"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier</wicri:regionArea>
<orgName type="university">Université de Trèves</orgName>
<placeName><settlement type="city">Trèves (Allemagne)</settlement>
<region type="land" nuts="1">Rhénanie-Palatinat</region>
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</affiliation>
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<author><name sortKey="Gilsbach, Susanne" sort="Gilsbach, Susanne" uniqKey="Gilsbach S" first="Susanne" last="Gilsbach">Susanne Gilsbach</name>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Aix-la-Chapelle</settlement>
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<author><name sortKey="Herpertz Ahlmann, Beate" sort="Herpertz Ahlmann, Beate" uniqKey="Herpertz Ahlmann B" first="Beate" last="Herpertz-Dahlmann">Beate Herpertz-Dahlmann</name>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Aix-la-Chapelle</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sinzig, Judith" sort="Sinzig, Judith" uniqKey="Sinzig J" first="Judith" last="Sinzig">Judith Sinzig</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne</wicri:regionArea>
<wicri:noRegion>Cologne</wicri:noRegion>
<wicri:noRegion>Cologne</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lehmkuhl, Gerd" sort="Lehmkuhl, Gerd" uniqKey="Lehmkuhl G" first="Gerd" last="Lehmkuhl">Gerd Lehmkuhl</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne</wicri:regionArea>
<wicri:noRegion>Cologne</wicri:noRegion>
<wicri:noRegion>Cologne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Renner, Tobias J" sort="Renner, Tobias J" uniqKey="Renner T" first="Tobias J." last="Renner">Tobias J. Renner</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg</wicri:regionArea>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Warnke, Andreas" sort="Warnke, Andreas" uniqKey="Warnke A" first="Andreas" last="Warnke">Andreas Warnke</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg</wicri:regionArea>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Romanos, Marcel" sort="Romanos, Marcel" uniqKey="Romanos M" first="Marcel" last="Romanos">Marcel Romanos</name>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lesch, Klaus Eter" sort="Lesch, Klaus Eter" uniqKey="Lesch K" first="Klaus-Peter" last="Lesch">Klaus-Peter Lesch</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg</wicri:regionArea>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Reif, Andreas" sort="Reif, Andreas" uniqKey="Reif A" first="Andreas" last="Reif">Andreas Reif</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg</wicri:regionArea>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
<wicri:noRegion>Wuerzburg</wicri:noRegion>
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</author>
<author><name sortKey="Schimmelmann, Benno G" sort="Schimmelmann, Benno G" uniqKey="Schimmelmann B" first="Benno G." last="Schimmelmann">Benno G. Schimmelmann</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><country xml:lang="fr">Suisse</country>
<wicri:regionArea>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern</wicri:regionArea>
<placeName><settlement type="city">Berne</settlement>
<region type="région" nuts="3">Canton de Berne</region>
</placeName>
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</author>
<author><name sortKey="Hebebrand, Johannes" sort="Hebebrand, Johannes" uniqKey="Hebebrand J" first="Johannes" last="Hebebrand">Johannes Hebebrand</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
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<monogr></monogr>
<series><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title>
<title level="j" type="abbrev">Am. J. Med. Genet.</title>
<idno type="ISSN">1552-4841</idno>
<idno type="eISSN">1552-485X</idno>
<imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher>
<pubPlace>Hoboken</pubPlace>
<date type="published" when="2011-12">2011-12</date>
<biblScope unit="volume">156</biblScope>
<biblScope unit="issue">8</biblScope>
<biblScope unit="page" from="888">888</biblScope>
<biblScope unit="page" to="897">897</biblScope>
</imprint>
<idno type="ISSN">1552-4841</idno>
</series>
<idno type="istex">E2378FE797C80441EE8EF5CBC324FFFC2CE70D67</idno>
<idno type="DOI">10.1002/ajmg.b.31246</idno>
<idno type="ArticleID">AJMG31246</idno>
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<seriesStmt><idno type="ISSN">1552-4841</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Association</term>
<term>Attention disorder with hyperactivity</term>
<term>Child</term>
<term>Early</term>
<term>Genome</term>
<term>Germany</term>
<term>Human</term>
<term>Patient</term>
<term>children</term>
<term>early onset</term>
<term>homogeneous</term>
<term>psychiatric</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Allemagne</term>
<term>Association</term>
<term>Enfant</term>
<term>Génome</term>
<term>Homme</term>
<term>Malade</term>
<term>Précoce</term>
<term>Trouble déficitaire de l'attention avec hyperactivité</term>
</keywords>
<keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Allemagne</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Association</term>
<term>Enfant</term>
<term>Homme</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
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</teiHeader>
<front><div type="abstract" xml:lang="en">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. © 2011 Wiley Periodicals, Inc.</div>
</front>
</TEI>
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<name sortKey="Jarick, Ivonne" sort="Jarick, Ivonne" uniqKey="Jarick I" first="Ivonne" last="Jarick">Ivonne Jarick</name>
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<name sortKey="Nguyen, Trang T" sort="Nguyen, Trang T" uniqKey="Nguyen T" first="Trang T." last="Nguyen">Trang T. Nguyen</name>
<name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M." last="Nöthen">Markus M. Nöthen</name>
<name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M." last="Nöthen">Markus M. Nöthen</name>
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<name sortKey="Putter, Carolin" sort="Putter, Carolin" uniqKey="Putter C" first="Carolin" last="Pütter">Carolin Pütter</name>
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<name sortKey="Sinzig, Judith" sort="Sinzig, Judith" uniqKey="Sinzig J" first="Judith" last="Sinzig">Judith Sinzig</name>
<name sortKey="Volckmar, Anna Ena" sort="Volckmar, Anna Ena" uniqKey="Volckmar A" first="Anna-Lena" last="Volckmar">Anna-Lena Volckmar</name>
<name sortKey="Warnke, Andreas" sort="Warnke, Andreas" uniqKey="Warnke A" first="Andreas" last="Warnke">Andreas Warnke</name>
<name sortKey="Weber, Heike" sort="Weber, Heike" uniqKey="Weber H" first="Heike" last="Weber">Heike Weber</name>
<name sortKey="Wichmann, H Rich" sort="Wichmann, H Rich" uniqKey="Wichmann H" first="H. Rich" last="Wichmann">H. Rich Wichmann</name>
</country>
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<name sortKey="Schimmelmann, Benno G" sort="Schimmelmann, Benno G" uniqKey="Schimmelmann B" first="Benno G." last="Schimmelmann">Benno G. Schimmelmann</name>
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<name sortKey="Neale, Benjamin M" sort="Neale, Benjamin M" uniqKey="Neale B" first="Benjamin M." last="Neale">Benjamin M. Neale</name>
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<country name="Pays-Bas"><region name="Gueldre"><name sortKey="Franke, Barbara" sort="Franke, Barbara" uniqKey="Franke B" first="Barbara" last="Franke">Barbara Franke</name>
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