This title appears in the Scientific Report : 2016 

Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
Li, Ming (Corresponding author)
Huang, Liang / Grigoroiu-Serbanescu, Maria (Corresponding author) / Bergen, Sarah E / Landén, Mikael / Hultman, Christina M / Forstner, Andreas J / Strohmaier, Jana / Hecker, Julian / Schulze, Thomas G / Müller-Myhsok, Bertram / Reif, Andreas / Mitchell, Philip B / Martin, Nicholas G / Cichon, Sven / Nöthen, Markus M / Alkelai, Anna / Lerer, Bernard / Jamain, Stéphane / Leboyer, Marion / Bellivier, Frank / Etain, Bruno / Kahn, Jean-Pierre / Henry, Chantal / Rietschel, Marcella / Consortium, MooDS (Collaboration Author) / Group, Swedish Bipolar Study (Collaboration Author)
Strukturelle und funktionelle Organisation des Gehirns; INM-1
Molecular neurobiology, 53 (2016) 10, S. 6608–6619
Totowa, NJ Humana Press 2016
Journal Article
Connectivity and Activity
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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.