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Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.

Artikel i vetenskaplig tidskrift
Författare 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
Publicerad i Molecular neurobiology
Volym 53
Nummer/häfte 10
Sidor 6608–6619
ISSN 1559-1182
Publiceringsår 2016
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 6608–6619
Språk en
Länkar dx.doi.org/10.1007/s12035-015-9559-...
Ämneskategorier Neurovetenskaper

Sammanfattning

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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