Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26637325
TITLE
Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.
ABSTRACT
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.
DATE PUBLISHED
2015 Dec 4
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Li M Li Ming M 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 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 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Forstner AJ Forstner Andreas J AJ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Strohmaier J Strohmaier Jana J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Hecker J Hecker Julian J Institute of Genomic Mathematics, University of Bonn, Bonn, Germany.
Schulze TG Schulze Thomas G TG Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.
Müller-Myhsok B Müller-Myhsok Bertram B Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Reif A Reif Andreas A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Mitchell PB Mitchell Philip B PB Black Dog Institute, Sydney, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Cichon S Cichon Sven S 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 Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Alkelai A Alkelai Anna A 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 Université Paris Diderot, Paris, France.
Etain B Etain Bruno B AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France.
Kahn JP Kahn Jean-Pierre JP Département de Psychiatrie et de Psychologie Clinique, CHU de Nancy, Hôpital Jeanne d'Arc, Toul, France.
Henry C Henry Chantal C AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France.
Rietschel M Rietschel Marcella M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
MooDS Consortium
Swedish Bipolar Study Group
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular neurobiology
ISOABBREVIATION: Mol. Neurobiol.
YEAR: 2015
MONTH: Dec
DAY: 4
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1559-1182
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Neurobiol
COUNTRY:
ISSNLINKING: 0893-7648
NLMUNIQUEID: 8900963
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Bipolar disorder
LRP8
Schizophrenia
mRNA expression
rs5174
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's