Convergent lines of evidence support LRP8 as a susceptibility gene for psychosis

• Verfasst von: Li, Ming [VerfasserIn]
• Verfasst von: Rietschel, Marcella [VerfasserIn]
• Titel: Convergent lines of evidence support LRP8 as a susceptibility gene for psychosis
• Verf.angabe: 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. Nöthen, 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
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 12 S.
• Fussnoten: Gesehen am 27.03.2019 ; Published online: 4 December 2015
• Titel Quelle: Enthalten in: Molecular neurobiology
• Ort Quelle: Totowa, NJ : Humana Press, 1987
• Jahr Quelle: 2016
• Band/Heft Quelle: 53(2016), 10, Seite 6608-6619
• ISSN Quelle: 1559-1182
• DOI: doi:10.1007/s12035-015-9559-6
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Bipolar disorder
• Sach-SW: LRP8
• Sach-SW: mRNA expression
• Sach-SW: rs5174
• Sach-SW: Schizophrenia
• K10plus-PPN: 1662463235

Abstract

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.