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| PMID |
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| TITLE |
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| Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis. |
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| ABSTRACT |
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NlmCategory: UNASSIGNED |
| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2015/08/26 |
| accepted |
2015/11/22 |
| aheadofprint |
2015/12/04 |
| entrez |
2015/12/06 06:00 |
| pubmed |
2015/12/08 06:00 |
| medline |
2015/12/08 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Li M |
|
Li |
Ming |
M |
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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. |
| Huang L |
|
Huang |
Liang |
L |
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First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China. |
| Grigoroiu-Serbanescu M |
|
Grigoroiu-Serbanescu |
Maria |
M |
|
Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. maria.serbanescu@googlemail.com. |
| Bergen SE |
|
Bergen |
Sarah E |
SE |
|
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. |
| Landén M |
|
Landén |
Mikael |
M |
|
Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden. |
| Hultman CM |
|
Hultman |
Christina M |
CM |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Forstner AJ |
|
Forstner |
Andreas J |
AJ |
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Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
| Strohmaier J |
|
Strohmaier |
Jana |
J |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany. |
| Hecker J |
|
Hecker |
Julian |
J |
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Institute of Genomic Mathematics, University of Bonn, Bonn, Germany. |
| Schulze TG |
|
Schulze |
Thomas G |
TG |
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Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany. |
| Müller-Myhsok B |
|
Müller-Myhsok |
Bertram |
B |
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Institute of Translational Medicine, University of Liverpool, Liverpool, UK. |
| Reif A |
|
Reif |
Andreas |
A |
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Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany. |
| Mitchell PB |
|
Mitchell |
Philip B |
PB |
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Black Dog Institute, Sydney, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Cichon S |
|
Cichon |
Sven |
S |
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Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Centre Jülich, D-52425, Jülich, Germany. |
| Nöthen MM |
|
Nöthen |
Markus M |
MM |
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Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
| Alkelai A |
|
Alkelai |
Anna |
A |
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Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. |
| Lerer B |
|
Lerer |
Bernard |
B |
|
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. |
| Jamain S |
|
Jamain |
Stéphane |
S |
|
Fondation Fondamental, Créteil, France. |
| Leboyer M |
|
Leboyer |
Marion |
M |
|
AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France. |
| Bellivier F |
|
Bellivier |
Frank |
F |
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Université Paris Diderot, Paris, France. |
| Etain B |
|
Etain |
Bruno |
B |
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AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France. |
| Kahn JP |
|
Kahn |
Jean-Pierre |
JP |
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Département de Psychiatrie et de Psychologie Clinique, CHU de Nancy, Hôpital Jeanne d'Arc, Toul, France. |
| Henry C |
|
Henry |
Chantal |
C |
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AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France. |
| Rietschel M |
|
Rietschel |
Marcella |
M |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany. |
|
MooDS Consortium |
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Swedish Bipolar Study Group |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Molecular neurobiology |
| ISOABBREVIATION: Mol. Neurobiol. |
| YEAR: 2015 |
| MONTH: Dec |
| DAY: 4 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1559-1182 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Mol Neurobiol |
| COUNTRY: United States |
| ISSNLINKING: 0893-7648 |
| NLMUNIQUEID: 8900963 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| JOURNAL ARTICLE |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| Bipolar disorder |
| LRP8 |
| Schizophrenia |
| mRNA expression |
| rs5174 |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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