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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 |
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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 |
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Huang |
Liang |
L |
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First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China. |
Grigoroiu-Serbanescu M |
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Grigoroiu-Serbanescu |
Maria |
M |
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Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. maria.serbanescu@googlemail.com. |
Bergen SE |
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Bergen |
Sarah E |
SE |
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Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. |
Landén M |
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Landén |
Mikael |
M |
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Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden. |
Hultman CM |
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Hultman |
Christina M |
CM |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
Forstner AJ |
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Forstner |
Andreas J |
AJ |
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Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
Strohmaier J |
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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 |
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Hecker |
Julian |
J |
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Institute of Genomic Mathematics, University of Bonn, Bonn, Germany. |
Schulze TG |
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Schulze |
Thomas G |
TG |
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Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany. |
Müller-Myhsok B |
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Müller-Myhsok |
Bertram |
B |
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Institute of Translational Medicine, University of Liverpool, Liverpool, UK. |
Reif A |
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Reif |
Andreas |
A |
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Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany. |
Mitchell PB |
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Mitchell |
Philip B |
PB |
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Black Dog Institute, Sydney, Australia. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Cichon S |
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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 |
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Nöthen |
Markus M |
MM |
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Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. |
Alkelai A |
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Alkelai |
Anna |
A |
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Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. |
Lerer B |
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Lerer |
Bernard |
B |
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Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. |
Jamain S |
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Jamain |
Stéphane |
S |
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Fondation Fondamental, Créteil, France. |
Leboyer M |
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Leboyer |
Marion |
M |
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AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France. |
Bellivier F |
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Bellivier |
Frank |
F |
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Université Paris Diderot, Paris, France. |
Etain B |
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Etain |
Bruno |
B |
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AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France. |
Kahn JP |
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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 |
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Henry |
Chantal |
C |
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AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France. |
Rietschel M |
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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. |
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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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OTHER ID's |
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