Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

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Association study between genetic variants at the PIP5K2A gene locus and schizophrenia and bipolar affective disorder.

Results from molecular and pharmacological studies point to involvement of the gene coding for the phosphatidylinositol-4-phosphate 5-kinase type II-alpha (PIP5K2A) in the development of schizophrenia and bipolar affective disorder (BPAD). The PIP5K2A gene locus, which is located on chromosomal region 10p12, has been implicated in the development of both disorders by independent linkage and association studies. On a cellular level, PIP5K2A is an enzyme component of the metabolism of inositol phosphate, which has been considered a potential target for the therapeutic action of lithium in BPAD patients. Given that the PIP5K2A gene is a promising candidate for the development of both disorders, we performed an association study between genetic variants at the PIP5K2A locus and 268 patients with schizophrenia, 260 patients with BPAD and 325 ethnically matched healthy controls. We failed to detect association to either disorder using PIP5K2A gene variants through single-marker and haplotype analysis. Therefore, our data does not support an involvement of the PIP5K2A locus in the etiology of either schizophrenia or BPAD in the German population. © 2006 Wiley-Liss, Inc

No association between genetic variants at the GRIN1 gene and bipolar disorder in a Germany sample.

Disturbed glutamatergic neurotransmission has been implicated in the pathogenesis of schizophrenia and bipolar disorder, with the N-methy-D-aspartate receptors being in the focus of research. The NR1 subunit, which is encoded by the gene GRIN1, plays a key role in the functionality of N-methy-D-aspartate receptors. We tested the association between GRIN1 and bipolar disorder in a sample of German descent, consisting of 306 bipolar disorder patients and 319 population-based controls. No significant association was found. In accordance with our recent findings, we hypothesized that restricting case definition to individuals with a history of persecutory delusions might clarify the relationship between bipolar disorder and GRIN1. This stratified analysis did not yield any significant association either. Our results do not support an association of the GRIN1 gene with bipolar disorder in the German population. © 2006 Lippincott Williams & Wilkins

No association between genetic variants at the ASCT1 gene and schizophrenia or bipolar disorder in a German sample.

Altered glutamatergic neurotransmission is considered a potential etiological factor of schizophrenia (SCZ) and affective disorders. The gene ASCT1 (SLC1A4) coding for a Na-dependent neutral aminoacid transporter is a member of the glutamate transporter superfamily and is located on 2p13-14, a region showing linkage to both SCZ and bipolar disorder (BD). ASCT1 can thus be considered a candidate gene for both disorders. In a German sample, we tested for association between ASCT1 and both SCZ and BD. Allele and haplotype frequencies, however, did not differ between cases and controls. Recent findings on the associations between brainderived neurotrophic factor (BDNF) and SCZ and between G72/G30 and BD suggest that SCZ patients with a history of major depressive episodes (MDE) outside psychotic episodes and BD cases with a history of persecutory delusions constitute genetically distinct subgroups of these disorders. Thus, we hypothesized that restricting case definition to those 95 SCZ individuals with MDE and to those 107 BD patients with a history of persecutory delusions might clarify the relationship between BD, SCZ and ASCT1. However, these stratification approaches did not yield any significant association either. Allele and haplotype frequencies did not differ between cases and controls. Our results do not support an association of the ASCT1 gene with BD or SCZ in the German population

Possible association between genetic variants at the GRIN1 gene and schizophrenia with lifetime history of depressive symptoms in a German sample.

Genetic variation in glutamatergic signalling pathways is believed to play a substantial role in the aetiology of schizophrenia. The N-methyl-D-aspartate receptor subunit gene GRIN1 has been proposed as a candidate gene for schizophrenia. We tested for a potential association between schizophrenia and four single nucleotide polymorphisms (rs4880213, rs11146020, rs6293, and rs10747050) and one microsatellite marker at GRIN1 in a German sample of 354 patients and 323 controls. We found significant associations in single-marker and haplotype-based analyses (P<0.05). Significance was more pronounced (P<0.01) in the subset of patients with a lifetime history of major depression, a subgroup of schizophrenia described previously as a promising phenotypic subtype in genetic studies of schizophrenia. Although significances did not withstand correction for multiple testing, the results of our exploratory analysis warrant further studies on GRIN1 and schizophrenia