No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample : Implications for Psychiatric Genetics
Identifieur interne : 008B65 ( Main/Exploration ); précédent : 008B64; suivant : 008B66No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample : Implications for Psychiatric Genetics
Auteurs : Alan R. Sanders [États-Unis, Australie, France] ; JUBAO DUAN ; Douglas F. Levinson ; JIANXIN SHI ; DELI HE ; CUIPING HOU ; Gregory J. Burrell ; John P. Rice ; Deborah A. Nertney ; Ann Olincy ; Pablo Rozic ; Sophia Vinogradov ; Nancy G. Buccola ; Bryan J. Mowry ; Robert Freedman ; Farooq Amin ; Donald W. Black ; Jeremy M. Silverman ; William F. Byerley ; Raymond R. Crowe ; C. Robert Cloninger ; Maria Martinez ; Pablo V. GejmanSource :
- The American journal of psychiatry [ 0002-953X ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Génétique, Santé publique, Santé mentale, Homme.
English descriptors
- KwdEn :
Abstract
Objective: The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide poly-morphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. Method: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3' untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Results: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. Conclusions: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.
Affiliations:
- Australie, France, États-Unis
- Californie, Iowa, Midi-Pyrénées, Occitanie (région administrative), État de New York
- San Francisco, Toulouse
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Gejman</name></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">08-0245861</idno><date when="2008">2008</date><idno type="stanalyst">PASCAL 08-0245861 INIST</idno><idno type="RBID">Pascal:08-0245861</idno><idno type="wicri:Area/PascalFrancis/Corpus">003590</idno><idno type="stanalyst">FRANCIS 08-0245861 INIST</idno><idno type="wicri:Area/PascalFrancis/Corpus">003855</idno><idno type="wicri:Area/PascalFrancis/Curation">002A57</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">003042</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">003042</idno><idno type="wicri:doubleKey">0002-953X:2008:Sanders A:no:significant:association</idno><idno type="wicri:Area/Main/Merge">009456</idno><idno type="wicri:Area/Main/Curation">008B65</idno><idno type="wicri:Area/Main/Exploration">008B65</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample : Implications for Psychiatric Genetics</title><author><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. 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, Ill</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>Evanston, Ill</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine</s1><s2>Palo Alto, Calif</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>Palo Alto, Calif</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Departments of Psychiatry and Genetics, Washington University</s1><s2>St. Louis</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>St. Louis</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Queensland Centre for Mental Health Research and the Queensland Institute for Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3></inist:fA14><country>Australie</country><wicri:noRegion>Queensland Centre for Mental Health Research and the Queensland Institute for Medical Research</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Psychiatry, University of Colorado Health Sciences Center</s1><s2>Denver</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>Denver</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>School of Nursing, Louisiana State University Health Sciences Center</s1><s2>New Orleans</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>New Orleans</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Atlanta Veterans Affairs Medical Center and Department of Psychiatry and Behavioral Sciences, Emory University</s1><s2>Atlanta</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>Atlanta</wicri:noRegion></affiliation><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa College of Medicine</s1><s2>Iowa City, Iowa</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Department of Psychiatry, Mount Sinai School of Medicine</s1><s2>New York</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Department of Psychiatry, University of California</s1><s2>San Francisco</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><placeName><settlement type="city">San Francisco</settlement><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Département de Génétique, INSERM-U563, Institut National de la Recherche et de la Santé Médicale</s1><s2>Toulouse</s2><s3>FRA</s3></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Jubao Duan" sort="Jubao Duan" uniqKey="Jubao Duan" last="Jubao Duan">JUBAO DUAN</name></author><author><name sortKey="Levinson, Douglas F" sort="Levinson, Douglas F" uniqKey="Levinson D" first="Douglas F." last="Levinson">Douglas F. Levinson</name></author><author><name sortKey="Jianxin Shi" sort="Jianxin Shi" uniqKey="Jianxin Shi" last="Jianxin Shi">JIANXIN SHI</name></author><author><name sortKey="Deli He" sort="Deli He" uniqKey="Deli He" last="Deli He">DELI HE</name></author><author><name sortKey="Cuiping Hou" sort="Cuiping Hou" uniqKey="Cuiping Hou" last="Cuiping Hou">CUIPING HOU</name></author><author><name sortKey="Burrell, Gregory J" sort="Burrell, Gregory J" uniqKey="Burrell G" first="Gregory J." last="Burrell">Gregory J. Burrell</name></author><author><name sortKey="Rice, John P" sort="Rice, John P" uniqKey="Rice J" first="John P." last="Rice">John P. Rice</name></author><author><name sortKey="Nertney, Deborah A" sort="Nertney, Deborah A" uniqKey="Nertney D" first="Deborah A." last="Nertney">Deborah A. Nertney</name></author><author><name sortKey="Olincy, Ann" sort="Olincy, Ann" uniqKey="Olincy A" first="Ann" last="Olincy">Ann Olincy</name></author><author><name sortKey="Rozic, Pablo" sort="Rozic, Pablo" uniqKey="Rozic P" first="Pablo" last="Rozic">Pablo Rozic</name></author><author><name sortKey="Vinogradov, Sophia" sort="Vinogradov, Sophia" uniqKey="Vinogradov S" first="Sophia" last="Vinogradov">Sophia Vinogradov</name></author><author><name sortKey="Buccola, Nancy G" sort="Buccola, Nancy G" uniqKey="Buccola N" first="Nancy G." last="Buccola">Nancy G. Buccola</name></author><author><name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J." last="Mowry">Bryan J. Mowry</name></author><author><name sortKey="Freedman, Robert" sort="Freedman, Robert" uniqKey="Freedman R" first="Robert" last="Freedman">Robert Freedman</name></author><author><name sortKey="Amin, Farooq" sort="Amin, Farooq" uniqKey="Amin F" first="Farooq" last="Amin">Farooq Amin</name></author><author><name sortKey="Black, Donald W" sort="Black, Donald W" uniqKey="Black D" first="Donald W." last="Black">Donald W. Black</name></author><author><name sortKey="Silverman, Jeremy M" sort="Silverman, Jeremy M" uniqKey="Silverman J" first="Jeremy M." last="Silverman">Jeremy M. Silverman</name></author><author><name sortKey="Byerley, William F" sort="Byerley, William F" uniqKey="Byerley W" first="William F." last="Byerley">William F. Byerley</name></author><author><name sortKey="Crowe, Raymond R" sort="Crowe, Raymond R" uniqKey="Crowe R" first="Raymond R." last="Crowe">Raymond R. Crowe</name></author><author><name sortKey="Cloninger, C Robert" sort="Cloninger, C Robert" uniqKey="Cloninger C" first="C. Robert" last="Cloninger">C. Robert Cloninger</name></author><author><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name></author><author><name sortKey="Gejman, Pablo V" sort="Gejman, Pablo V" uniqKey="Gejman P" first="Pablo V." last="Gejman">Pablo V. Gejman</name></author></analytic><series><title level="j" type="main">The American journal of psychiatry</title><title level="j" type="abbreviated">Am. j. psychiatr.</title><idno type="ISSN">0002-953X</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">The American journal of psychiatry</title><title level="j" type="abbreviated">Am. j. psychiatr.</title><idno type="ISSN">0002-953X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Candidate gene</term><term>Europe</term><term>Genetics</term><term>Human</term><term>Mental health</term><term>Progeny</term><term>Public health</term><term>Risk factor</term><term>Schizoaffective psychosis</term><term>Schizophrenia</term><term>Single nucleotide polymorphism</term><term>Social environment</term><term>United States</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Gène candidat</term><term>Schizophrénie</term><term>Génétique</term><term>Polymorphisme mononucléotide</term><term>Psychose schizoaffective</term><term>Facteur risque</term><term>Santé publique</term><term>Santé mentale</term><term>Environnement social</term><term>Etats-Unis</term><term>Descendance</term><term>Europe</term><term>Homme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term><term>Santé publique</term><term>Santé mentale</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide poly-morphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. Method: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3' untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Results: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. Conclusions: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>États-Unis</li></country><region><li>Californie</li><li>Iowa</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>État de New York</li></region><settlement><li>San Francisco</li><li>Toulouse</li></settlement></list><tree><noCountry><name sortKey="Amin, Farooq" sort="Amin, Farooq" uniqKey="Amin F" first="Farooq" last="Amin">Farooq Amin</name><name sortKey="Black, Donald W" sort="Black, Donald W" uniqKey="Black D" first="Donald W." last="Black">Donald W. Black</name><name sortKey="Buccola, Nancy G" sort="Buccola, Nancy G" uniqKey="Buccola N" first="Nancy G." last="Buccola">Nancy G. Buccola</name><name sortKey="Burrell, Gregory J" sort="Burrell, Gregory J" uniqKey="Burrell G" first="Gregory J." last="Burrell">Gregory J. Burrell</name><name sortKey="Byerley, William F" sort="Byerley, William F" uniqKey="Byerley W" first="William F." last="Byerley">William F. Byerley</name><name sortKey="Cloninger, C Robert" sort="Cloninger, C Robert" uniqKey="Cloninger C" first="C. Robert" last="Cloninger">C. Robert Cloninger</name><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="Deli He" sort="Deli He" uniqKey="Deli He" last="Deli He">DELI HE</name><name sortKey="Freedman, Robert" sort="Freedman, Robert" uniqKey="Freedman R" first="Robert" last="Freedman">Robert Freedman</name><name sortKey="Gejman, Pablo V" sort="Gejman, Pablo V" uniqKey="Gejman P" first="Pablo V." last="Gejman">Pablo V. Gejman</name><name sortKey="Jianxin Shi" sort="Jianxin Shi" uniqKey="Jianxin Shi" last="Jianxin Shi">JIANXIN SHI</name><name sortKey="Jubao Duan" sort="Jubao Duan" uniqKey="Jubao Duan" last="Jubao Duan">JUBAO DUAN</name><name sortKey="Levinson, Douglas F" sort="Levinson, Douglas F" uniqKey="Levinson D" first="Douglas F." last="Levinson">Douglas F. Levinson</name><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name><name sortKey="Mowry, Bryan J" sort="Mowry, Bryan J" uniqKey="Mowry B" first="Bryan J." last="Mowry">Bryan J. Mowry</name><name sortKey="Nertney, Deborah A" sort="Nertney, Deborah A" uniqKey="Nertney D" first="Deborah A." last="Nertney">Deborah A. Nertney</name><name sortKey="Olincy, Ann" sort="Olincy, Ann" uniqKey="Olincy A" first="Ann" last="Olincy">Ann Olincy</name><name sortKey="Rice, John P" sort="Rice, John P" uniqKey="Rice J" first="John P." last="Rice">John P. Rice</name><name sortKey="Rozic, Pablo" sort="Rozic, Pablo" uniqKey="Rozic P" first="Pablo" last="Rozic">Pablo Rozic</name><name sortKey="Silverman, Jeremy M" sort="Silverman, Jeremy M" uniqKey="Silverman J" first="Jeremy M." last="Silverman">Jeremy M. Silverman</name><name sortKey="Vinogradov, Sophia" sort="Vinogradov, Sophia" uniqKey="Vinogradov S" first="Sophia" last="Vinogradov">Sophia Vinogradov</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name></noRegion><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name></country><country name="Australie"><noRegion><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name></noRegion></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Sanders, Alan R" sort="Sanders, Alan R" uniqKey="Sanders A" first="Alan R." last="Sanders">Alan R. Sanders</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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