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Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
- Source :
- Molecular neurobiology. 53(10)
- Publication Year :
- 2015
-
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.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Linkage disequilibrium
Psychosis
Bipolar Disorder
Time Factors
Neuroscience (miscellaneous)
Single-nucleotide polymorphism
Genome-wide association study
Polymorphism, Single Nucleotide
Linkage Disequilibrium
03 medical and health sciences
Cellular and Molecular Neuroscience
Fetus
Gene Frequency
Risk Factors
Internal medicine
mental disorders
medicine
Odds Ratio
SNP
Chromosomes, Human
Humans
Genetic Predisposition to Disease
Bipolar disorder
Protein Interaction Maps
RNA, Messenger
LDL-Receptor Related Proteins
Genetics
Gene Expression Profiling
Brain
Odds ratio
medicine.disease
Reelin Protein
030104 developmental biology
Neurology
Psychotic Disorders
Schizophrenia
Psychology
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15591182
- Volume :
- 53
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology
- Accession number :
- edsair.doi.dedup.....b0863bc07bdfffa95b7eecbe5bd98be6