Combinations of genetic variants associated with bipolar disorder.

The main objective of the study was to find genetic variants that in combination are significantly associated with bipolar disorder. In previous studies of bipolar disorder, combinations of three and four single nucleotide polymorphisms (SNP) genotypes taken from 803 SNPs were analyzed, and five clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of ten SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder.

Combinations of SNP genotypes from the Wellcome Trust Case Control Study of bipolar patients.

Objectives: Combinations of genetic variants are the basis for polygenic disorders. We examined combinations of SNP genotypes taken from the 446 729 SNPs in The Wellcome Trust Case Control Study of bipolar patients.

Methods: Parallel computing by graphics processing units, cloud computing, and data mining tools were used to scan The Wellcome Trust data set for combinations.

Combinations of Genetic Variants Occurring Exclusively in Patients.

In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder.

Combinations of genetic data in a study of oral cancer.

In the single locus strategy a number of genetic variants are analyzed, in order to find variants that are distributed significantly different between controls and patients. A supplementary strategy is to analyze combinations of genetic variants. A combination that is the genetic basis for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients.

Combinations of Genetic Data Present in Bipolar Patients, but Absent in Control Persons.

The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder.

Combinations of genetic data in a study of neuroblastoma risk genotypes.

Analysis of combinations of genetic changes that occur exclusively in patients may be a supplementary strategy to the single-locus strategy used in many genetic studies. The genotypes of 16 SNPs within susceptibility loci for neuroblastoma (NB) were analyzed in a previous study. In the present study, combinations of these genotypes have been analyzed.

Connection between genetic and clinical data in bipolar disorder.

Complex diseases may be associated with combinations of changes in DNA, where the single change has little impact alone. In a previous study of patients with bipolar disorder and controls combinations of SNP genotypes were analyzed, and four large clusters of combinations were found to be significantly associated with bipolar disorder. It has now been found that these clusters may be connected to clinical data.

Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression.

Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.

Genetics of complex diseases: variations on a theme.

A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e.

Association analysis of ANK3 gene variants in nordic bipolar disorder and schizophrenia case-control samples.

Genetic variants in ankyrin 3 (ANK3) have recently been shown to be associated with bipolar disorder (BD). We genotyped three ANK3 SNPs previously found to be associated with BD (rs10994336, rs1938526, and rs9804190) in a Scandinavian BD case-control sample (N = 854/2,614). Due to evidence of genetic overlap between BD and schizophrenia (SZ), we also genotyped these three SNPs in a Scandinavian SZ case-control sample (N = 1,073/2,919).

Combinations of SNPs related to signal transduction in bipolar disorder.

Any given single nucleotide polymorphism (SNP) in a genome may have little or no functional impact. A biologically significant effect may possibly emerge only when a number of key SNP-related genotypes occur together in a single organism. Thus, in analysis of many SNPs in association studies of complex diseases, it may be useful to look at combinations of genotypes.

Meta-analysis of heterogeneous data sources for genome-scale identification of risk genes in complex phenotypes.

Meta-analyses of large-scale association studies typically proceed solely within one data type and do not exploit the potential complementarities in other sources of molecular evidence. Here, we present an approach to combine heterogeneous data from genome-wide association (GWA) studies, protein-protein interaction screens, disease similarity, linkage studies, and gene expression experiments into a multi-layered evidence network which is used to prioritize the entire protein-coding part of the genome identifying a shortlist of candidate genes. We report specifically results on bipolar disorder, a genetically complex disease where GWA studies have only been moderately successful.

Association analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample.

A recent genome-wide association study (GWAS) found significant association between the PALB2 SNP rs420259 and bipolar disorder (BD). The intracellular functions of the expressed proteins from the breast cancer risk genes PALB2 and BRCA2 are closely related. Therefore, we investigated the relation between genetic variants in PALB2 and BRCA2 and BD.

Variations in 5-HTTLPR: relation to familiar risk of affective disorder, life events, neuroticism and cortisol.

Background: Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders.

Aim: To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol.

Method: In a high-risk population study, healthy monozygotic and dizygotic twins with (high-risk twins) and without (low-risk twins) a co-twin history of affective disorder were identified through nationwide registers.

Risperidone treatment increases CB1 receptor binding in rat brain.

Background/aims: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB(1)), the serotonin receptor 2C, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone.

No association between DGKH and bipolar disorder in a Scandinavian case-control sample.

Single nucleotide polymorphisms (SNPs) in diacylglycerol kinase eta (DGKH) have recently been shown to be associated with bipolar disorder (BD). To replicate this finding, we carried out a gene-wide genotyping of 36 tagSNPs in DGKH and performed a population-based association study on two Scandinavian samples, with successful genotyping of 594 BD cases and 1421 healthy controls. We found no significant association after multiple-testing correction between any of these SNPs and BD in our sample.

Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1.

Bodyweight gain is a common side effect of treatment with antidepressive drugs; however, little is known about the mechanisms behind this weight gain. Genetic differences may contribute to the susceptibility for bodyweight gain during antidepressive treatment. The objective of this study was to examine the association of antidepressive-drug-induced bodyweight gain with polymorphisms in genes within the serotonin or catecholamine systems.

Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples.

The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect. We have genotyped and analyzed 40 and 72 tagging single nucleotide polymorphisms (tagSNPs) in SZ and BP multicenter samples, respectively, from the Scandinavian Collaboration on Psychiatric Etiology (SCOPE), involving 837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls.

The serotonin transporter and 5HT2A receptor in rat brain after localized lesions.

Objectives: Post-stroke depression and depression after traumatic brain lesion are most often seen when the lesion includes frontal areas. The development of depression may include the serotonergic system because selective serotonin reuptake inhibitors (SSRIs) can be used to treat the depression. The purpose of the present study was to examine whether serotonin transporter density or 5HT2A serotonin receptor density is changed in specific brain areas following anterior or posterior lesions in the two hemispheres.

Association of the 5-HT2A receptor gene polymorphism 102T/C with ischemic stroke.

Serotonin (5-HT) has been implicated in a number of cardiovascular disorders due to its ability to induce vascular contraction and platelet aggregation through activation of the 5-HT2 receptor family. In this study, we investigated the association of stroke in a Scandinavian population with two common polymorphisms in the 5-HT2A receptor gene. The two polymorphisms under investigation, namely the 102T/C and the -1438A/G variations of the 5-HT2A receptor gene, were examined in a case control association study involving 99 stroke patients and a comparable number of controls.

No association between the -399 C > T polymorphism of the neuropeptide Y gene and schizophrenia, unipolar depression or panic disorder in a Danish population.

Objective: A polymorphism in the promoter region of the NPY gene at position -399 C > T was recently reported to be associated with schizophrenia in a Japanese population and with treatment refractory unipolar depression in a Swedish population. The objective of this study was to investigate potential associations between the polymorphism and three psychiatric disorders in a Danish population.

Method: We investigated the occurrence of the polymorphism in patients with schizophrenia (n = 291), unipolar depression (n = 256) and panic disorder (n = 142) compared with controls (n = 716).

Mania as a dysfunction of reentry: application of Edelman's and Tononi's hypothesis for consciousness in relation to a psychiatric disorder.

The concept of reentry as the most important element in a hypothesis for consciousness proposed by Edelman and Tononi is reviewed. Reentry, is a process of ongoing parallel and recursive signalling between separate neuronal groups along parallel reciprocally fibers that link these groups anatomically. Reentry alters the activity of the target areas it interconnects until a synchronous activity across these areas is created, this may be the direct biological mechanism of consciousness.

Different roles of 5-HT2A and 5-HT2C receptors in regulation of female rat paced mating behaviour.

Serotonin (5-HT) receptor 2A (5-HT2A) and 2C (5-HT2C) agonists have been reported to facilitate female rat lordosis behaviour. This study investigated the acute effects of the 5-HT2A receptor agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and the 5-HT2C receptor agonist MK-212 (2-chloro-6-(1-piperazinyl) pyrazine) on paced mating behaviour in a population of sexually receptive female rats in order to explore the role of 5-HT2A and 5-HT2C receptors in the mediation of female rat sexual motivation. DOI (0.

Associative and nonassociative learning after chronic imipramine in rats.

We investigated effects of 15 daily injections of imipramine (20 mg/kg; in one experiment also 10 and 30 mg/kg). The associative learning types (place learning and object recognition) as well as nonassociative learning (habituation of exploration in an open field and within the object recognition test) were studied. Tests were performed immediately after the final injection (early test) and 24 h after the final injection (late test).