The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia
S C Bakker1, M L C Hoogendoorn, J Hendriks
1Department of Psychiatry, University Medical Center, Utrecht, the Netherlands. s.c.bakker@med.uu.nl
Genes, Brain, and Behavior
|April 6, 2007
Summary
This study investigated schizophrenia susceptibility genes in patients with and without deficit schizophrenia. The PIP5K2A gene showed the strongest association with both schizophrenia subtypes, suggesting its role in the disorder.
Area of Science:
- Genetics
- Psychiatry
- Molecular Biology
Background:
- Schizophrenia susceptibility genes are being identified, but their association with specific disease subtypes remains unclear.
- Previous research linked neuregulin 1 (NRG1) to non-deficit schizophrenia.
- Deficit schizophrenia is characterized by severe, enduring negative symptoms.
Purpose of the Study:
- To investigate the association of four schizophrenia candidate genes (DTNBP1, G72/G30, RGS4, and PIP5K2A) with deficit and non-deficit schizophrenia subtypes.
- To explore the role of PIP5K2A, located in a linkage region for schizophrenia and bipolar disorder, as a potential susceptibility gene.
Main Methods:
- Genotyping of single-nucleotide polymorphisms (SNPs) in DTNBP1, G72/G30, RGS4, and PIP5K2A.
- Analysis of 273 Dutch schizophrenia patients (146 with deficit schizophrenia) and 580 controls.
- Association analysis of SNPs and haplotypes with schizophrenia subtypes.
Main Results:
- The strongest association was found for the A-allele of PIP5K2A SNP rs10828317 in both deficit and non-deficit schizophrenia subtypes (P = 0.0004).
- This PIP5K2A SNP leads to a change in protein composition.
- The G-allele of RGS4 SNP RGS4-1 was associated with non-deficit schizophrenia (P = 0.03) but not deficit schizophrenia (P = 0.79).
- No significant associations were found for DTNBP1 and G72/G30 genes.
Conclusions:
- Specific genes may be implicated in different schizophrenia subtypes.
- The PIP5K2A gene warrants further investigation as a general susceptibility gene for schizophrenia.
- Genetic variations in PIP5K2A could contribute to the pathophysiology of schizophrenia.
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