机构：[1]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.[2]First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.[3]Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. maria.[4]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.[5]Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.[6]Section of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.[7]Institute of Human Genetics, University of Bonn, Bonn, Germany.[8]Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.[9]Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.[10]Institute of Genomic Mathematics, University of Bonn, Bonn, Germany.[11]Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.[12]Max Planck Institute of Psychiatry, Munich, Germany.[13]Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.[14]Institute of Translational Medicine, University of Liverpool, Liverpool, UK.[15]Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.[16]School of Psychiatry, University of New South Wales, Sydney, Australia.[17]Black Dog Institute, Sydney, Australia.[18]QIMR Berghofer Medical Research Institute, Brisbane, Australia.[19]Division of Medical Genetics, University Hospital Basel and Department of Biomedicine, University of Basel, Basel, Switzerland.[20]Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Centre Jülich, D-52425, Jülich, Germany.[21]Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.[22]Inserm U 955, IMRB, Psychiatrie Translationnelle, Créteil, France.[23]Université Paris Est, Faculté de Médecine, Créteil, France.[24]Fondation Fondamental, Créteil, France.[25]AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, Créteil, France.[26]AP-HP, Groupe hospitalier Lariboisière - F. Widal, Pôle de Psychiatrie, Paris, France.[27]Université Paris Diderot, Paris, France.[28]Département de Psychiatrie et de Psychologie Clinique, CHU de Nancy, Hôpital Jeanne d'Arc, Toul, France.
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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出版当年[2016]版：
大类|2 区医学
小类|2 区神经科学
最新[2023]版：
大类|2 区医学
小类|2 区神经科学
第一作者：
第一作者机构：[1]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.
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推荐引用方式(GB/T 7714)：
Li Ming,Huang Liang,Grigoroiu-Serbanescu Maria,et al.Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis[J].Molecular neurobiology.2016,53(10):6608-6619.doi:10.1007/s12035-015-9559-6.
APA：
Li Ming,Huang Liang,Grigoroiu-Serbanescu Maria,Bergen Sarah E,Landén Mikael...&MooDS Consortium & The Swedish Bipolar Study Group.(2016).Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.Molecular neurobiology,53,(10)
MLA：
Li Ming,et al."Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis".Molecular neurobiology 53..10(2016):6608-6619
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