Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.
Identifieur interne : 002163 ( Main/Exploration ); précédent : 002162; suivant : 002164Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.
Auteurs : Ming Li [République populaire de Chine] ; Liang Huang [République populaire de Chine] ; Maria Grigoroiu-Serbanescu [Roumanie] ; Sarah E. Bergen [Suède] ; Mikael Landén [Suède] ; Christina M. Hultman [Suède] ; Andreas J. Forstner [Allemagne] ; Jana Strohmaier [Allemagne] ; Julian Hecker [Allemagne] ; Thomas G. Schulze [Allemagne] ; Bertram Müller-Myhsok [Allemagne] ; Andreas Reif [Allemagne] ; Philip B. Mitchell [Australie] ; Nicholas G. Martin [Australie] ; Sven Cichon [Allemagne] ; Markus M. Nöthen [Allemagne] ; Anna Alkelai [Israël] ; Bernard Lerer [Israël] ; Stéphane Jamain [France] ; Marion Leboyer [France] ; Frank Bellivier [France] ; Bruno Etain [France] ; Jean-Pierre Kahn [France] ; Chantal Henry [France] ; Marcella Rietschel [Allemagne]Source :
- Molecular neurobiology [ 1559-1182 ] ; 2016.
Abstract
Reelin (RELN) is identified as a risk gene for major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). However, the role of its downstream signaling molecule, the low-density lipoprotein receptor-related protein 8 (LRP8) in these illnesses is still unclear. To detect whether LRP8 is a susceptibility gene for SCZ and BPD, we analyzed the associations of single nucleotide polymorphisms (SNPs) in LRP8 in a total of 47,187 subjects (including 9379 SCZ patients; 6990 BPD patients; and 12,556 controls in a screening sample, and 1397 SCZ families, 3947 BPD patients, and 8387 controls in independent replications), and identified a non-synonymous SNP rs5174 in LRP8 significantly associated with SCZ and BPD as well as the combined psychosis phenotype (P meta = 1.99 × 10(-5), odds ratio (OR) = 1.066, 95 % confidence interval (CI) = 1.035-1.098). The risk SNP rs5174 was also associated with LRP8 messenger RNA (mRNA) expression in multiple brain tissues across independent samples (lowest P = 0.00005). Further exploratory analysis revealed that LRP8 was preferentially expressed in fetal brain tissues. Protein-protein interaction (PPI) analysis demonstrated that LRP8 significantly participated in a highly interconnected PPI network build by top risk genes for SCZ and BPD (P = 7.0 × 10(-4)). Collectively, we confirmed that LRP8 is a risk gene for psychosis, and our results provide useful information toward a better understanding of genetic mechanism involving LRP8 underlying risk of complex psychiatric disorders.
DOI: 10.1007/s12035-015-9559-6
PubMed: 26637325
Affiliations:
- Allemagne, Australie, France, Israël, Roumanie, République populaire de Chine, Suède
- Bade-Wurtemberg, Bavière, District de Cologne, District de Darmstadt, District de Haute-Bavière, District de Karlsruhe, Hesse (Land), Nouvelle-Galles du Sud, Rhénanie-du-Nord-Westphalie, Svealand, Île-de-France
- Bonn, Créteil, Francfort-sur-le-Main, Heidelberg, Munich, Stockholm, Sydney
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Schulze</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University 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="Muller Myhsok, Bertram" sort="Muller Myhsok, Bertram" uniqKey="Muller Myhsok B" first="Bertram" last="Müller-Myhsok">Bertram Müller-Myhsok</name><affiliation wicri:level="3"><nlm:affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max Planck Institute of Psychiatry, 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="Reif, Andreas" sort="Reif, Andreas" uniqKey="Reif A" first="Andreas" last="Reif">Andreas Reif</name><affiliation wicri:level="3"><nlm:affiliation>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt</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="Mitchell, Philip B" sort="Mitchell, Philip B" uniqKey="Mitchell P" first="Philip B" last="Mitchell">Philip B. 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Nöthen</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, 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></placeName></affiliation></author><author><name sortKey="Alkelai, Anna" sort="Alkelai, Anna" uniqKey="Alkelai A" first="Anna" last="Alkelai">Anna Alkelai</name><affiliation wicri:level="1"><nlm:affiliation>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem</wicri:regionArea><wicri:noRegion>Jerusalem</wicri:noRegion></affiliation></author><author><name sortKey="Lerer, Bernard" sort="Lerer, Bernard" uniqKey="Lerer B" first="Bernard" last="Lerer">Bernard Lerer</name><affiliation wicri:level="1"><nlm:affiliation>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem</wicri:regionArea><wicri:noRegion>Jerusalem</wicri:noRegion></affiliation></author><author><name sortKey="Jamain, Stephane" sort="Jamain, Stephane" uniqKey="Jamain S" first="Stéphane" last="Jamain">Stéphane Jamain</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, 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type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Kahn, Jean Pierre" sort="Kahn, Jean Pierre" uniqKey="Kahn J" first="Jean-Pierre" last="Kahn">Jean-Pierre Kahn</name><affiliation wicri:level="3"><nlm:affiliation>Fondation Fondamental, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Fondation Fondamental, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Henry, Chantal" sort="Henry, Chantal" uniqKey="Henry C" first="Chantal" last="Henry">Chantal Henry</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Rietschel, Marcella" sort="Rietschel, Marcella" uniqKey="Rietschel M" first="Marcella" last="Rietschel">Marcella Rietschel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement 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type="wicri:Area/Main/Exploration">002163</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.</title><author><name sortKey="Li, Ming" sort="Li, Ming" uniqKey="Li M" first="Ming" last="Li">Ming Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. limingkiz@gmail.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan</wicri:regionArea><wicri:noRegion>Yunnan</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Liang" sort="Huang, Liang" uniqKey="Huang L" first="Liang" last="Huang">Liang Huang</name><affiliation wicri:level="1"><nlm:affiliation>First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi</wicri:regionArea><wicri:noRegion>Jiangxi</wicri:noRegion></affiliation></author><author><name sortKey="Grigoroiu Serbanescu, Maria" sort="Grigoroiu Serbanescu, Maria" uniqKey="Grigoroiu Serbanescu M" first="Maria" last="Grigoroiu-Serbanescu">Maria Grigoroiu-Serbanescu</name><affiliation wicri:level="1"><nlm:affiliation>Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. maria.serbanescu@googlemail.com.</nlm:affiliation><country xml:lang="fr">Roumanie</country><wicri:regionArea>Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest</wicri:regionArea><wicri:noRegion>Bucharest</wicri:noRegion></affiliation></author><author><name sortKey="Bergen, Sarah E" sort="Bergen, Sarah E" uniqKey="Bergen S" first="Sarah E" last="Bergen">Sarah E. Bergen</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Landen, Mikael" sort="Landen, Mikael" uniqKey="Landen M" first="Mikael" last="Landén">Mikael Landén</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Hultman, Christina M" sort="Hultman, Christina M" uniqKey="Hultman C" first="Christina M" last="Hultman">Christina M. Hultman</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Forstner, Andreas J" sort="Forstner, Andreas J" uniqKey="Forstner A" first="Andreas J" last="Forstner">Andreas J. Forstner</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, 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></placeName></affiliation></author><author><name sortKey="Strohmaier, Jana" sort="Strohmaier, Jana" uniqKey="Strohmaier J" first="Jana" last="Strohmaier">Jana Strohmaier</name><affiliation wicri:level="3"><nlm:affiliation>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hecker, Julian" sort="Hecker, Julian" uniqKey="Hecker J" first="Julian" last="Hecker">Julian Hecker</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, 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></placeName></affiliation></author><author><name sortKey="Schulze, Thomas G" sort="Schulze, Thomas G" uniqKey="Schulze T" first="Thomas G" last="Schulze">Thomas G. Schulze</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University 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="Muller Myhsok, Bertram" sort="Muller Myhsok, Bertram" uniqKey="Muller Myhsok B" first="Bertram" last="Müller-Myhsok">Bertram Müller-Myhsok</name><affiliation wicri:level="3"><nlm:affiliation>Max Planck Institute of Psychiatry, Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max Planck Institute of Psychiatry, 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="Reif, Andreas" sort="Reif, Andreas" uniqKey="Reif A" first="Andreas" last="Reif">Andreas Reif</name><affiliation wicri:level="3"><nlm:affiliation>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt</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="Mitchell, Philip B" sort="Mitchell, Philip B" uniqKey="Mitchell P" first="Philip B" last="Mitchell">Philip B. Mitchell</name><affiliation wicri:level="3"><nlm:affiliation>School of Psychiatry, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Psychiatry, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation wicri:level="1"><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Cichon, Sven" sort="Cichon, Sven" uniqKey="Cichon S" first="Sven" last="Cichon">Sven Cichon</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, 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></placeName></affiliation></author><author><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M" last="Nöthen">Markus M. Nöthen</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, 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></placeName></affiliation></author><author><name sortKey="Alkelai, Anna" sort="Alkelai, Anna" uniqKey="Alkelai A" first="Anna" last="Alkelai">Anna Alkelai</name><affiliation wicri:level="1"><nlm:affiliation>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem</wicri:regionArea><wicri:noRegion>Jerusalem</wicri:noRegion></affiliation></author><author><name sortKey="Lerer, Bernard" sort="Lerer, Bernard" uniqKey="Lerer B" first="Bernard" last="Lerer">Bernard Lerer</name><affiliation wicri:level="1"><nlm:affiliation>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem</wicri:regionArea><wicri:noRegion>Jerusalem</wicri:noRegion></affiliation></author><author><name sortKey="Jamain, Stephane" sort="Jamain, Stephane" uniqKey="Jamain S" first="Stéphane" last="Jamain">Stéphane Jamain</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Leboyer, Marion" sort="Leboyer, Marion" uniqKey="Leboyer M" first="Marion" last="Leboyer">Marion Leboyer</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Bellivier, Frank" sort="Bellivier, Frank" uniqKey="Bellivier F" first="Frank" last="Bellivier">Frank Bellivier</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Etain, Bruno" sort="Etain, Bruno" uniqKey="Etain B" first="Bruno" last="Etain">Bruno Etain</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Kahn, Jean Pierre" sort="Kahn, Jean Pierre" uniqKey="Kahn J" first="Jean-Pierre" last="Kahn">Jean-Pierre Kahn</name><affiliation wicri:level="3"><nlm:affiliation>Fondation Fondamental, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Fondation Fondamental, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Henry, Chantal" sort="Henry, Chantal" uniqKey="Henry C" first="Chantal" last="Henry">Chantal Henry</name><affiliation wicri:level="3"><nlm:affiliation>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Créteil</settlement></placeName></affiliation></author><author><name sortKey="Rietschel, Marcella" sort="Rietschel, Marcella" uniqKey="Rietschel M" first="Marcella" last="Rietschel">Marcella Rietschel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></analytic><series><title level="j">Molecular neurobiology</title><idno type="eISSN">1559-1182</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Reelin (RELN) is identified as a risk gene for major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). However, the role of its downstream signaling molecule, the low-density lipoprotein receptor-related protein 8 (LRP8) in these illnesses is still unclear. To detect whether LRP8 is a susceptibility gene for SCZ and BPD, we analyzed the associations of single nucleotide polymorphisms (SNPs) in LRP8 in a total of 47,187 subjects (including 9379 SCZ patients; 6990 BPD patients; and 12,556 controls in a screening sample, and 1397 SCZ families, 3947 BPD patients, and 8387 controls in independent replications), and identified a non-synonymous SNP rs5174 in LRP8 significantly associated with SCZ and BPD as well as the combined psychosis phenotype (P meta = 1.99 × 10(-5), odds ratio (OR) = 1.066, 95 % confidence interval (CI) = 1.035-1.098). The risk SNP rs5174 was also associated with LRP8 messenger RNA (mRNA) expression in multiple brain tissues across independent samples (lowest P = 0.00005). Further exploratory analysis revealed that LRP8 was preferentially expressed in fetal brain tissues. Protein-protein interaction (PPI) analysis demonstrated that LRP8 significantly participated in a highly interconnected PPI network build by top risk genes for SCZ and BPD (P = 7.0 × 10(-4)). Collectively, we confirmed that LRP8 is a risk gene for psychosis, and our results provide useful information toward a better understanding of genetic mechanism involving LRP8 underlying risk of complex psychiatric disorders.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Israël</li><li>Roumanie</li><li>République populaire de Chine</li><li>Suède</li></country><region><li>Bade-Wurtemberg</li><li>Bavière</li><li>District de Cologne</li><li>District de Darmstadt</li><li>District de Haute-Bavière</li><li>District de Karlsruhe</li><li>Hesse (Land)</li><li>Nouvelle-Galles du Sud</li><li>Rhénanie-du-Nord-Westphalie</li><li>Svealand</li><li>Île-de-France</li></region><settlement><li>Bonn</li><li>Créteil</li><li>Francfort-sur-le-Main</li><li>Heidelberg</li><li>Munich</li><li>Stockholm</li><li>Sydney</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Ming" sort="Li, Ming" uniqKey="Li M" first="Ming" last="Li">Ming Li</name></noRegion><name sortKey="Huang, Liang" sort="Huang, Liang" uniqKey="Huang L" first="Liang" last="Huang">Liang Huang</name></country><country name="Roumanie"><noRegion><name sortKey="Grigoroiu Serbanescu, Maria" sort="Grigoroiu Serbanescu, Maria" uniqKey="Grigoroiu Serbanescu M" first="Maria" last="Grigoroiu-Serbanescu">Maria Grigoroiu-Serbanescu</name></noRegion></country><country name="Suède"><region name="Svealand"><name sortKey="Bergen, Sarah E" sort="Bergen, Sarah E" uniqKey="Bergen S" first="Sarah E" last="Bergen">Sarah E. Bergen</name></region><name sortKey="Hultman, Christina M" sort="Hultman, Christina M" uniqKey="Hultman C" first="Christina M" last="Hultman">Christina M. Hultman</name><name sortKey="Landen, Mikael" sort="Landen, Mikael" uniqKey="Landen M" first="Mikael" last="Landén">Mikael Landén</name></country><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Forstner, Andreas J" sort="Forstner, Andreas J" uniqKey="Forstner A" first="Andreas J" last="Forstner">Andreas J. Forstner</name></region><name sortKey="Cichon, Sven" sort="Cichon, Sven" uniqKey="Cichon S" first="Sven" last="Cichon">Sven Cichon</name><name sortKey="Hecker, Julian" sort="Hecker, Julian" uniqKey="Hecker J" first="Julian" last="Hecker">Julian Hecker</name><name sortKey="Muller Myhsok, Bertram" sort="Muller Myhsok, Bertram" uniqKey="Muller Myhsok B" first="Bertram" last="Müller-Myhsok">Bertram Müller-Myhsok</name><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M" last="Nöthen">Markus M. Nöthen</name><name sortKey="Reif, Andreas" sort="Reif, Andreas" uniqKey="Reif A" first="Andreas" last="Reif">Andreas Reif</name><name sortKey="Rietschel, Marcella" sort="Rietschel, Marcella" uniqKey="Rietschel M" first="Marcella" last="Rietschel">Marcella Rietschel</name><name sortKey="Schulze, Thomas G" sort="Schulze, Thomas G" uniqKey="Schulze T" first="Thomas G" last="Schulze">Thomas G. Schulze</name><name sortKey="Strohmaier, Jana" sort="Strohmaier, Jana" uniqKey="Strohmaier J" first="Jana" last="Strohmaier">Jana Strohmaier</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Mitchell, Philip B" sort="Mitchell, Philip B" uniqKey="Mitchell P" first="Philip B" last="Mitchell">Philip B. Mitchell</name></region><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name></country><country name="Israël"><noRegion><name sortKey="Alkelai, Anna" sort="Alkelai, Anna" uniqKey="Alkelai A" first="Anna" last="Alkelai">Anna Alkelai</name></noRegion><name sortKey="Lerer, Bernard" sort="Lerer, Bernard" uniqKey="Lerer B" first="Bernard" last="Lerer">Bernard Lerer</name></country><country name="France"><region name="Île-de-France"><name sortKey="Jamain, Stephane" sort="Jamain, Stephane" uniqKey="Jamain S" first="Stéphane" last="Jamain">Stéphane Jamain</name></region><name sortKey="Bellivier, Frank" sort="Bellivier, Frank" uniqKey="Bellivier F" first="Frank" last="Bellivier">Frank Bellivier</name><name sortKey="Etain, Bruno" sort="Etain, Bruno" uniqKey="Etain B" first="Bruno" last="Etain">Bruno Etain</name><name sortKey="Henry, Chantal" sort="Henry, Chantal" uniqKey="Henry C" first="Chantal" last="Henry">Chantal Henry</name><name sortKey="Kahn, Jean Pierre" sort="Kahn, Jean Pierre" uniqKey="Kahn J" first="Jean-Pierre" last="Kahn">Jean-Pierre Kahn</name><name sortKey="Leboyer, Marion" sort="Leboyer, Marion" uniqKey="Leboyer M" first="Marion" last="Leboyer">Marion Leboyer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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