Journal Article

FZJ-2016-00175

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

Li, M. (Corresponding author) ; Huang, L. ; Grigoroiu-Serbanescu, M. (Corresponding author) ; Bergen, S. E. ; Landén, M. ; Hultman, C. M. ; Forstner, A. J. ; Strohmaier, J. ; Hecker, J. ; Schulze, T. G. ; Müller-Myhsok, B. ; Reif, A. ; Mitchell, P. B. ; Martin, N. G. ; Cichon, S.FZJ* ; Nöthen, M. M. ; Alkelai, A. ; Lerer, B. ; Jamain, S. ; Leboyer, M. ; Bellivier, F. ; Etain, B. ; Kahn, J.-P. ; Henry, C. ; Rietschel, M. ; Consortium, M. (Collaboration Author) ; Group, S. B. S. (Collaboration Author)

2016
Humana Press Totowa, NJ

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Please use a persistent id in citations: doi:10.1007/s12035-015-9559-6

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.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. 571 - Connectivity and Activity (POF3-571) (POF3-571)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; No Authors Fulltext ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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