Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

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	Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
	Li M[]1; Huang L 2; Hultman CM 4; Forstner AJ 7,8; Strohmaier J 9; Hecker J 7,10; Schulze TG 11; Müller-Myhsok B 12,13,14; Grigoroiu-Serbanescu M[]3; Reif A 15
刊名	Molecular Neurobiology
	2015
卷号	53 期号:X 页码:6608–6619
关键词	Bipolar disorder LRP8 Schizophrenia mRNA expression rs5174
通讯作者	limingkiz@gmail.com.maria.serbanescu@googlemail.com
合作状况	其它
英文摘要	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.
收录类别	SCI
资助信息	This work was supported by the German Federal Ministry of Education and Research (BMBF) throughtheIntegratedGenomeResearchNetwork(IG)MooDS(System- atic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia; grant 01GS08144 to SC and MMN, grant 01GS08147 to MR), under the auspices of the National Genome Research Network plus (NGFNplus), and through the Integrated Network IntegraMent (Integrat- ed Understanding of Causes and Mechanisms in Mental Disorders), un- der the auspices of the e: Med Programme (grant 01ZX1314A to SC and MMN, grant 01ZX1314G to MR).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9504]
专题	昆明动物研究所_转化基因组昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	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. 4.Max Planck Institute of Psychiatry, Munich, Germany 5.Munich Cluster for Systems Neurology (SyNergy), Munich, Germany 6.Institute of Translational Medicine, University of Liverpool, Liverpool, UK. 7.Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany 8.School of Psychiatry, University of New South Wales, Sydney, Australia. 9.Black Dog Institute, Sydney, Australia 10.QIMR Berghofer Medical Research Institute, Brisbane, Australia
推荐引用方式 GB/T 7714	Li M[*],Huang L,Hultman CM,et al. Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis[J]. Molecular Neurobiology,2015,53(X):6608–6619.
APA	Li M[*].,Huang L.,Hultman CM.,Forstner AJ.,Strohmaier J.,...&Landén M.(2015).Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.Molecular Neurobiology,53(X),6608–6619.
MLA	Li M[*],et al."Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis".Molecular Neurobiology 53.X(2015):6608–6619.