Polymorphisms in the Trace Amine Receptor 4 (TRAR4) Gene on Chromosome 6q23.2 Are Associated with Susceptibility to Schizophrenia
Identifieur interne : 000115 ( Ncbi/Merge ); précédent : 000114; suivant : 000116Polymorphisms in the Trace Amine Receptor 4 (TRAR4) Gene on Chromosome 6q23.2 Are Associated with Susceptibility to Schizophrenia
Auteurs : Jubao Duan [États-Unis] ; Maria Martinez [France] ; Alan R. Sanders [États-Unis] ; Cuiping Hou [États-Unis] ; Naruya Saitou [Japon] ; Takashi Kitano [Japon] ; Bryan J. Mowry ; Raymond R. Crowe ; Jeremy M. Silverman [États-Unis] ; Douglas F. Levinson [États-Unis] ; Pablo V. Gejman [États-Unis]Source :
- American Journal of Human Genetics [ 0002-9297 ] ; 2004.
Abstract
Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia—and, more recently, for bipolar disorder—on chromosome 6q13-q26. We genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the
Url:
PubMed: 15329799
PubMed Central: 1182049
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) Gene on Chromosome 6q23.2 Are Associated with Susceptibility to Schizophrenia</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Polymorphisms in the <italic>Trace Amine Receptor 4</italic>
(<italic>TRAR4</italic>
) Gene on Chromosome 6q23.2 Are Associated with Susceptibility to Schizophrenia</title>
<author><name sortKey="Duan, Jubao" sort="Duan, Jubao" uniqKey="Duan J" first="Jubao" last="Duan">Jubao Duan</name>
<affiliation wicri:level="2"><nlm:aff id="N0x9728040.0x8b59e80">Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University, Evanston, IL;</nlm:aff>
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<author><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
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<wicri:regionArea>Méthodologie Statistique et Epidémiologie Génétique des Maladies Multifactorielles, INSERM, Evry</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name>
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</affiliation>
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<author><name sortKey="Gejman, Pablo V" sort="Gejman, Pablo V" uniqKey="Gejman P" first="Pablo V." last="Gejman">Pablo V. Gejman</name>
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<front><div type="abstract" xml:lang="en"><p>Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia—and, more recently, for bipolar disorder—on chromosome 6q13-q26. We genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the <italic>MOXD1</italic>
-<italic>STX7</italic>
-<italic>TRARs</italic>
gene cluster at 6q23.2, which contains a number of prime candidate genes for schizophrenia. Thirty-one screening single-nucleotide polymorphisms (SNPs) were selected, providing a minimum coverage of at least 1 SNP/20 kb. The association observed with rs4305745 (<inline-formula><italic>P</italic>
=.0014</inline-formula>
) within the <italic>TRAR4</italic>
(<italic>trace amine receptor 4</italic>
) gene remained significant after correction for multiple testing. Evidence for association was proportionally stronger in the smaller AA sample. We performed database searches and sequenced genomic DNA in a 30-proband subsample to obtain a high-density map of 23 SNPs spanning 21.6 kb of this gene. Single-SNP analyses and also haplotype analyses revealed that rs4305745 and/or two other polymorphisms in perfect linkage disequilibrium (LD) with rs4305745 appear to be the most likely variants underlying the association of the <italic>TRAR4</italic>
region with schizophrenia. Comparative genomic analyses further revealed that rs4305745 and/or the associated polymorphisms in complete LD with rs4305745 could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirm that <italic>TRAR4</italic>
is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that <italic>TRAR4</italic>
is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.</p>
</div>
</front>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Hum Genet</journal-id>
<journal-id journal-id-type="publisher-id">AJHG</journal-id>
<journal-title>American Journal of Human Genetics</journal-title>
<issn pub-type="ppub">0002-9297</issn>
<issn pub-type="epub">1537-6605</issn>
<publisher><publisher-name>The American Society of Human Genetics</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">15329799</article-id>
<article-id pub-id-type="pmc">1182049</article-id>
<article-id pub-id-type="publisher-id">41399</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>Polymorphisms in the <italic>Trace Amine Receptor 4</italic>
(<italic>TRAR4</italic>
) Gene on Chromosome 6q23.2 Are Associated with Susceptibility to Schizophrenia</article-title>
<alt-title><italic>TRAR4</italic>
Association with Schizophrenia</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Duan</surname>
<given-names>Jubao</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Martinez</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sanders</surname>
<given-names>Alan R.</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hou</surname>
<given-names>Cuiping</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Saitou</surname>
<given-names>Naruya</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kitano</surname>
<given-names>Takashi</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mowry</surname>
<given-names>Bryan J.</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">4,5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Crowe</surname>
<given-names>Raymond R.</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Silverman</surname>
<given-names>Jeremy M.</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Levinson</surname>
<given-names>Douglas F.</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gejman</surname>
<given-names>Pablo V.</given-names>
</name>
<xref ref-type="aff" rid="N0x9728040.0x8b59e80">1</xref>
</contrib>
</contrib-group>
<aff id="N0x9728040.0x8b59e80"><sup>1</sup>
Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University, Evanston, IL;<sup>2</sup>
Méthodologie Statistique et Epidémiologie Génétique des Maladies Multifactorielles, INSERM, Evry, France;<sup>3</sup>
Division of Population Genetics, National Institute of Genetics, Mishima, Japan;<sup>4</sup>
Queensland Centre for Schizophrenia Research, The Park, Centre for Mental Health, Wacol, Australia;<sup>5</sup>
Department of Psychiatry, University of Queensland, Brisbane, Australia;<sup>6</sup>
Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa College of Medicine, Iowa City;<sup>7</sup>
Department of Psychiatry, Mount Sinai School of Medicine, New York; and<sup>8</sup>
Department of Psychiatry, University of Pennsylvania, Philadelphia</aff>
<author-notes><corresp>Address for correspondence and reprints: Dr. Pablo V. Gejman, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201-3137. E-mail: <email>pgejman@northwestern.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>10</month>
<year>2004</year>
</pub-date>
<pub-date pub-type="epub"><day>24</day>
<month>8</month>
<year>2004</year>
</pub-date>
<volume>75</volume>
<issue>4</issue>
<fpage>624</fpage>
<lpage>638</lpage>
<history><date date-type="received"><day>28</day>
<month>5</month>
<year>2004</year>
</date>
<date date-type="accepted"><day>23</day>
<month>7</month>
<year>2004</year>
</date>
</history>
<copyright-statement>© 2004 by The American Society of Human Genetics. All rights reserved.</copyright-statement>
<copyright-year>2004</copyright-year>
<self-uri>15329799</self-uri>
<abstract><p>Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia—and, more recently, for bipolar disorder—on chromosome 6q13-q26. We genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the <italic>MOXD1</italic>
-<italic>STX7</italic>
-<italic>TRARs</italic>
gene cluster at 6q23.2, which contains a number of prime candidate genes for schizophrenia. Thirty-one screening single-nucleotide polymorphisms (SNPs) were selected, providing a minimum coverage of at least 1 SNP/20 kb. The association observed with rs4305745 (<inline-formula><italic>P</italic>
=.0014</inline-formula>
) within the <italic>TRAR4</italic>
(<italic>trace amine receptor 4</italic>
) gene remained significant after correction for multiple testing. Evidence for association was proportionally stronger in the smaller AA sample. We performed database searches and sequenced genomic DNA in a 30-proband subsample to obtain a high-density map of 23 SNPs spanning 21.6 kb of this gene. Single-SNP analyses and also haplotype analyses revealed that rs4305745 and/or two other polymorphisms in perfect linkage disequilibrium (LD) with rs4305745 appear to be the most likely variants underlying the association of the <italic>TRAR4</italic>
region with schizophrenia. Comparative genomic analyses further revealed that rs4305745 and/or the associated polymorphisms in complete LD with rs4305745 could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirm that <italic>TRAR4</italic>
is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that <italic>TRAR4</italic>
is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.</p>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>France</li>
<li>Japon</li>
<li>États-Unis</li>
</country>
<region><li>Illinois</li>
<li>Pennsylvanie</li>
<li>État de New York</li>
<li>Île-de-France</li>
</region>
<settlement><li>Philadelphie</li>
<li>Évry (Essonne)</li>
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<tree><noCountry><name sortKey="Crowe, Raymond R" sort="Crowe, Raymond R" uniqKey="Crowe R" first="Raymond R." last="Crowe">Raymond R. Crowe</name>
<name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J." last="Mowry">Bryan J. Mowry</name>
</noCountry>
<country name="États-Unis"><region name="Illinois"><name sortKey="Duan, Jubao" sort="Duan, Jubao" uniqKey="Duan J" first="Jubao" last="Duan">Jubao Duan</name>
</region>
<name sortKey="Gejman, Pablo V" sort="Gejman, Pablo V" uniqKey="Gejman P" first="Pablo V." last="Gejman">Pablo V. Gejman</name>
<name sortKey="Hou, Cuiping" sort="Hou, Cuiping" uniqKey="Hou C" first="Cuiping" last="Hou">Cuiping Hou</name>
<name sortKey="Levinson, Douglas F" sort="Levinson, Douglas F" uniqKey="Levinson D" first="Douglas F." last="Levinson">Douglas F. Levinson</name>
<name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name>
<name sortKey="Silverman, Jeremy M" sort="Silverman, Jeremy M" uniqKey="Silverman J" first="Jeremy M." last="Silverman">Jeremy M. Silverman</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
</region>
</country>
<country name="Japon"><noRegion><name sortKey="Saitou, Naruya" sort="Saitou, Naruya" uniqKey="Saitou N" first="Naruya" last="Saitou">Naruya Saitou</name>
</noRegion>
<name sortKey="Kitano, Takashi" sort="Kitano, Takashi" uniqKey="Kitano T" first="Takashi" last="Kitano">Takashi Kitano</name>
</country>
</tree>
</affiliations>
</record>
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