Polymorphisms in the Trace Amine Receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia
Identifieur interne : 00AB43 ( Main/Exploration ); précédent : 00AB42; suivant : 00AB44Polymorphisms 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 [Australie] ; Raymond R. Crowe [États-Unis] ; Jeremy M. Silverman [États-Unis] ; Douglas F. Levinson [États-Unis] ; Pablo V. Gejman [États-Unis]Source :
- American journal of human genetics [ 0002-9297 ] ; 2004.
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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 MOXD1-STX7-TRARs 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 (P = .0014) within the TRAR4 (trace amine receptor 4) 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 TRAR4 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 TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that TRAR4 is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.
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Affiliations:
- Australie, France, Japon, États-Unis
- Pennsylvanie, État de New York, Île-de-France
- Philadelphie, Évry (Essonne)
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Sanders</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University</s1><s2>Evanston, IL</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Evanston, IL</wicri:noRegion></affiliation></author><author><name sortKey="Cuiping Hou" sort="Cuiping Hou" uniqKey="Cuiping Hou" last="Cuiping Hou">CUIPING HOU</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University</s1><s2>Evanston, IL</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Evanston, IL</wicri:noRegion></affiliation></author><author><name sortKey="Saitou, Naruya" sort="Saitou, Naruya" uniqKey="Saitou N" first="Naruya" last="Saitou">Naruya Saitou</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Population Genetics, National Institute of Genetics</s1><s2>Mishima</s2><s3>JPN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Mishima</wicri:noRegion></affiliation></author><author><name sortKey="Kitano, Takashi" sort="Kitano, Takashi" uniqKey="Kitano T" first="Takashi" last="Kitano">Takashi Kitano</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Population Genetics, National Institute of Genetics</s1><s2>Mishima</s2><s3>JPN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Mishima</wicri:noRegion></affiliation></author><author><name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J." last="Mowry">Bryan J. Mowry</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Queensland Centre for Schizophrenia Research, The Park, Centre for Mental Health</s1><s2>Wacol</s2><s3>AUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Wacol</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry, University of Queensland</s1><s2>Brisbane</s2><s3>AUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Crowe, Raymond R" sort="Crowe, Raymond R" uniqKey="Crowe R" first="Raymond R." last="Crowe">Raymond R. Crowe</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa College of Medicine</s1><s2>Iowa City</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Iowa City</wicri:noRegion></affiliation></author><author><name sortKey="Silverman, Jeremy M" sort="Silverman, Jeremy M" uniqKey="Silverman J" first="Jeremy M." last="Silverman">Jeremy M. Silverman</name><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Psychiatry, Mount Sinai School of Medicine</s1><s2>New York</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Levinson, Douglas F" sort="Levinson, Douglas F" uniqKey="Levinson D" first="Douglas F." last="Levinson">Douglas F. Levinson</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Department of Psychiatry, University of Pennsylvania</s1><s2>Philadelphia</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Philadelphie</settlement><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Gejman, Pablo V" sort="Gejman, Pablo V" uniqKey="Gejman P" first="Pablo V." last="Gejman">Pablo V. Gejman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University</s1><s2>Evanston, IL</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Evanston, IL</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amine</term><term>Biological receptor</term><term>Chromosome 4</term><term>Chromosome B4</term><term>Chromosome C6</term><term>Gene</term><term>Genetic determinism</term><term>Genetic mapping</term><term>Genetics</term><term>Human</term><term>Pathogenesis</term><term>Polymorphism</term><term>Predisposition</term><term>Schizophrenia</term><term>Sensitivity</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Schizophrénie</term><term>Polymorphisme</term><term>Amine</term><term>Récepteur biologique</term><term>Chromosome 4</term><term>Chromosome B4</term><term>Gène</term><term>Chromosome C6</term><term>Carte génétique</term><term>Sensibilité</term><term>Pathogénie</term><term>Déterminisme génétique</term><term>Prédisposition</term><term>Génétique</term><term>Homme</term><term>Association génétique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 MOXD1-STX7-TRARs 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 (P = .0014) within the TRAR4 (trace amine receptor 4) 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 TRAR4 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 TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that TRAR4 is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Japon</li><li>États-Unis</li></country><region><li>Pennsylvanie</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Philadelphie</li><li>Évry (Essonne)</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Duan, Jubao" sort="Duan, Jubao" uniqKey="Duan J" first="Jubao" last="Duan">Jubao Duan</name></noRegion><name sortKey="Crowe, Raymond R" sort="Crowe, Raymond R" uniqKey="Crowe R" first="Raymond R." last="Crowe">Raymond R. Crowe</name><name sortKey="Cuiping Hou" sort="Cuiping Hou" uniqKey="Cuiping Hou" last="Cuiping Hou">CUIPING HOU</name><name sortKey="Gejman, Pablo V" sort="Gejman, Pablo V" uniqKey="Gejman P" first="Pablo V." last="Gejman">Pablo V. Gejman</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><country name="Australie"><noRegion><name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J." last="Mowry">Bryan J. Mowry</name></noRegion><name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J." last="Mowry">Bryan J. Mowry</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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