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 (Pmeta = 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-12 |
| Number of pages | 12 |
| Journal | Molecular Neurobiology |
| DOIs | |
| State | Accepted/In press - Dec 4 2015 |
| Externally published | Yes |
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Keywords
- Bipolar disorder
- LRP8
- mRNA expression
- rs5174
- Schizophrenia
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
Cite this
Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis. / Li, Ming; Huang, Liang; Grigoroiu-Serbanescu, Maria; 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; Moods Consortium, Consortium; The Swedish Bipolar Study Group, Swedish Bipolar Study Group.
In: Molecular Neurobiology, 04.12.2015, p. 1-12.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
AU - Li, Ming
AU - Huang, Liang
AU - Grigoroiu-Serbanescu, Maria
AU - Bergen, Sarah E.
AU - Landén, Mikael
AU - Hultman, Christina M.
AU - Forstner, Andreas J.
AU - Strohmaier, Jana
AU - Hecker, Julian
AU - Schulze, Thomas G.
AU - Müller-Myhsok, Bertram
AU - Reif, Andreas
AU - Mitchell, Philip B.
AU - Martin, Nicholas G.
AU - Cichon, Sven
AU - Nöthen, Markus M.
AU - Alkelai, Anna
AU - Lerer, Bernard
AU - Jamain, Stéphane
AU - Leboyer, Marion
AU - Bellivier, Frank
AU - Etain, Bruno
AU - Kahn, Jean Pierre
AU - Henry, Chantal
AU - Rietschel, Marcella
AU - Moods Consortium, Consortium
AU - The Swedish Bipolar Study Group, Swedish Bipolar Study Group
PY - 2015/12/4
Y1 - 2015/12/4
N2 - 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 (Pmeta = 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.
AB - 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 (Pmeta = 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.
KW - Bipolar disorder
KW - LRP8
KW - mRNA expression
KW - rs5174
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84949490917&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949490917&partnerID=8YFLogxK
U2 - 10.1007/s12035-015-9559-6
DO - 10.1007/s12035-015-9559-6
M3 - Article
C2 - 26637325
AN - SCOPUS:84949490917
SP - 1
EP - 12
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
ER -