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论文 |
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| 论文题目: |
Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis |
| 作者: |
Ming Li* , Liang Huang , Maria Grigoroiu-Serbanescu* , Sarah E. Bergen, Mikael Landén, Christina M. Hultman, Andreas J. Forstner, Jana Strohmaier, Julian Hecker, Thomas G. Schulze, Bertram Müller-Myhsok, Andreas Reif, Philip B. Mitchell, Nicholas G. Martin, Sven Cichon, Markus M. N？then, Anna Alkelai, Bernard Lerer, Stéphane Jamain, Marion Leboyer, Frank Bellivier, Bruno Etain, Jean-Pierre Kahn, Chantal Henry, Marcella Rietschel, MooDS Consortium, The Swedish Bipolar Study Group |
| 联系作者: |
limingkiz@gmail.com |
| 发表年度: |
2015 |
| DOI: |
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| 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. |
| 刊物名称: |
Molecular Neurobiology |
| 论文出处: |
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| 影响因子: |
5.137 (2014) |
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