期刊
MOLECULAR NEUROBIOLOGY
卷 53, 期 10, 页码 6608-6619出版社
SPRINGER
DOI: 10.1007/s12035-015-9559-6
关键词
LRP8; rs5174; Schizophrenia; Bipolar disorder; mRNA expression
资金
- German Federal Ministry of Education and Research (BMBF) [01GS08144, 01GS08147]
- Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e: Med Programme [01ZX1314A, 01ZX1314G]
- DFG
- UEFISCDI, Bucharest, Romania [89/2012]
- German Federal Ministry of Education and Research (BMBF), MooDS Project [01GS08144]
- Stanley Center for Psychiatric Research, Broad Institute Stanley Medical Research Institute
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 x 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 x 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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