M C O'Donovan

..Three studies have previously reported data that were interpreted by the authors as supportive of association between schizophrenia and polymorphisms in the gene encoding the metabotropic glutamate receptor GRM3...

..Two studies showed that subjects with the low activity Met allele performed better on the Wisconsin Card Sorting Test (WCST) and another study found an effect on processing speed and attention...

..They also provide grounds for optimism that larger studies will reveal more about the origins of these disorders, although currently, very little of the genetic risk of either disorder is explained...

..17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia...

..No pathogenic triplet repeat has yet been unambiguously implicated...

..However, the evidence across all approaches suggests that further study of this locus is warranted...

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..The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder...

..We conclude that our sample does not provide independent statistically significant evidence for association between GDNF and schizophrenia, nor does it replicate previous specific reports of association...

..These results suggest that any contribution of PCDH8 polymorphisms to schizophrenia susceptibility is likely to be weak, although the existence of rare variations of stronger effect cannot be excluded...

..35, P = 0.006, P = 0.078 corrected for 13 alleles)...

..05). Our results suggest it is unlikely that sequence variants in the Homer genes contribute to the aetiology of schizophrenia, but the variants we identified are plausible candidates for other neuropsychiatric phenotypes...

..05 level. These results do not suggest that PRODH or PsPRODH contribute to the aetiology of schizophrenia, and that the putative schizophrenia susceptibility gene in 22q11 remains unknown...

..Our results do not support the hypothesis that moderately rare non-synonymous variants at the ZNF804A locus are involved in schizophrenia susceptibility. © 2010 Wiley-Liss, Inc...

..820, P = 0.047, 1-tail). Our data therefore provide modest support for the hypothesis that polymorphism in the hKCa3 gene may contribute to susceptibility to schizophrenia...

..Our method of phenotype refinement may be useful in studies of other complex psychiatric and non-psychiatric disorders...

..Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for schizophrenia and overlapping susceptibility for bipolar disorder...

..Our analyses show that association signals are enriched in and around genes, large numbers of genes contribute to both disorders and gene-wide analyses offer useful complementary approaches to more standard methods...

..05, with the best result at P=1.2 x 10(-6) for rs11064768. This SNP is within the gene CCDC60, a coiled-coil domain gene. The third best SNP (P=0.00016) is rs893703, within RBP1, a candidate gene for schizophrenia...

..Recent research suggests that variation in the gene encoding dystrobrevin binding protein (DTNBP1) confers susceptibility to schizophrenia. Thus far, no specific risk haplotype has been identified in more than 1 study...

..As these are the only clear cut functional candidate genes in the region, identification of the putative susceptibility locus for RD on 15q will require more methodical non-hypothesis driven positional cloning approaches...

..Significant evidence for association of psychotic symptoms within cases was identified for two SNPs, rs762237 (allelic P=0.002, OR=1.42, corrected P=0.019) and rs2834072 (allelic P=0.004, OR=1.41, corrected P=0.05)...

..The most significant statistical interaction is between rs3740473, a synonymous single nucleotide polymorphism (SNP) in SH3MD1 and rs11244787, an intronic SNP in ADAM12 (effect size = 2.1 for interaction term, P = 0.006)...

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..Taken as a whole, this data demonstrate that if DTNBP1 is a risk gene for schizophrenia then risk is not conferred by mutations that affect the structure of the dysbindin protein...

..In sequencing exon 11 in 506 cases and 1,211 controls for variants that occurred only once, 4 additional rare variants were found in cases (P-value?=?0.008, Fisher's exact trend test)...

..2). These SNPs will therefore be suitable for studying neuropsychiatric phenotypes that are putatively related to NMDA dysfunction. Pooled analysis provided no support for association between any of the GRIN genes and schizophrenia...

..These results indicate that the up-regulation of dopamine receptors may be associated with the occurrence of tardive dyskinesia but not the clinical mode of action of antipsychotics...

..The polymorphisms identified in this study will be useful in examining the role of this gene in other neuropsychiatric disorders and behavioural traits...

..027, allelic P = 0.066). However this association was in the opposite direction to that detected in the Japanese population. It remains to be determined whether DNMBP is associated with LOAD...

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..Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological-genetic research...

..Therefore very rare, low-to-moderate penetrance protein coding mutations or non-coding mutations at DLG1 and/or PAK2, or a nearby gene, may reproduce the behavioral characteristics of the 3q29 microdeletion...

..Two SNPs in SGPL1 demonstrated marginal evidence of association, with uncorrected P values of 0.042 and 0.056, suggesting that variation in SGPL1 may confer susceptibility to LOAD...

..No evidence was found for the involvement of variants within the CUX2 coding, or 5' UTR sequence in producing susceptibility to bipolar disorder...

..001), where some of the variance was accounted for by the genotype at ss24735177. Our findings thus indicate the potential functional relevance of the associated haplotype and now require replication in independent samples...

..There may be evidence of G x E on associated antisocial behavior in ADHD, but further investigation is needed...

..We conclude that DHPLC is a highly sensitive and specific method for mutation detection...

..6%; P=0.019). Our results therefore replicate the Icelandic findings in an out-bred Northern European population, although they suggest that the risk conferred by the haplotype is small...

..Analysis of allele and genotype distributions for all six variations, and of haplotype frequencies showed no evidence for the involvement of ATP2A2 in producing susceptibility to bipolar disorder...

..The identification of these, and other susceptibility genes, will open up new avenues for research aimed at understanding the pathogenesis of schizophrenia, and will catalyse a re-appraisal of the classification of psychiatric disorders...

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..These findings support the hypothesis that psychotic symptoms in AD are genetically modified and that a gene/s implicated in their aetiology may be located on chromosome 7 and 15...

..In the absence of detailed knowledge about the genetic architecture at complex disease loci, we developed a mathematical approach to test all possible situations...

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..Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing...

..These data suggest that genetic variants affecting STS expression and/or activity could influence the function of brain regions perturbed in ADHD...

..No evidence for association of CTG18.1, ERDA1 and/or TGC13-7a with schizophrenia was found. The combined data accounted for only 54% of the CAG/CTG arrays of > 40 repeats found in our previous RED analysis...

..In this review, we consider the current state of evidence and the implications both for further studies of COMT and more generally for studies of other genes...

..Future directions in schizophrenia research include collecting larger samples to increase power of findings and applying novel methods for large-scale genotyping of single-nucleotide polymorphisms...

..In addition, our results provide support for association analysis being a useful method to map susceptibility loci for complex disorders...

..Future identification of psychosis susceptibility genes will have a major impact on our understanding of disease pathophysiology and will lead to changes in classification and the clinical practice of psychiatry...

..We also conclude that up-regulation of the D5 receptor is not likely to be involved in the mechanism of action of antipsychotic drugs...

..Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can, in principle, allow relevant susceptibility eQTLs to be identified...

..14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, ARC complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia...

..The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that it is now poised to deliver crucial insights into the nature of schizophrenia...

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..Both long and short mRNA variants were increased in abundance by approximately 2-fold by both haloperidol and loxapine after 32 days drug administration...

..The results from this study imply that neither the coding nor the regulatory region of DRD3 plays a major role in predisposition to schizophrenia...

..63 (df 3) P = 0.65). We conclude that the 3' VNTR and three additional promoter variants in DAT1 do not appear to be associated with ADHD, or response to stimulant mediation in our sample...

..These findings have implications for pathogenesis and nosology of schizophrenia and related disorders, and for future genetic studies...

..The purpose of this study was to identify the specific expanded CAG/CTG trinucleotide repeat associated with bipolar disorder...

..This supports the hypothesis that the DD gene has pleiotropic effects in brain and that mutations in SERCA2 are implicated in the pathogenesis of neuropsychiatric disorders...