Nigel M Williams

..Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology...

..However, other explanations are possible, and further analyses will be required to clarify the correct functional mechanism...

....

..However, although a number of genes have been implicated as possible schizophrenia susceptibility loci, further confirmatory studies are required...

....

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

....

..We aimed to establish whether burden of CNVs was increased in ADHD, and to investigate whether identified CNVs were enriched for loci previously identified in autism and schizophrenia...

..Microarray expression analysis may identify new candidate genes and pathways, and a number of intriguing preliminary findings have already been reported...

..We wished to investigate further the involvement of NRG1 in schizophrenia and bipolar disorder...

..The authors examined these hypotheses...

..Variation at the DAOA/G30 locus has been described to be associated with both schizophrenia and bipolar disorder, but there is little consistency between studies of the tested polymorphisms or variants showing association...

....

..Examination of our own data and those of other groups leads us to conclude that overall, the evidence for association of AKT1 as a susceptibility gene for schizophrenia is weakly positive, but not yet convincing...

..However, it is unclear whether the observed changes in the schizophrenic brain are primary or secondary...

..Our data, therefore, do not support the hypothesis that genetic variation in MAOA and COMT is involved individually or in combination in the etiology of schizophrenia...

..The ECM glycosaminoglycan hyaluronan (HA) influences TGF-b1 generation and can modulate its signal transduction activity; renal HA is synthesised by HA synthases HAS2 and HAS3...

..SLC1A3 is thus both a functional and positional candidate gene for ADHD...

..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...

..Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9))...

..Our data indicate that variation in the DTNBP1 gene confers susceptibility to schizophrenia through reduced expression, and that this, therefore, represents a primary aetiological mechanism in the disorder...

..At present there are no genome-wide significant linkage results for these phenotypes, but a number of suggestive findings warrant further investigation...

..It has been recently reported that a functional variant in the ZDHHC8 gene encoding a putative palmitoyltransferase directly confers susceptibility to schizophrenia in females ()...

..Although the original report was highly suggestive, a limitation was that the study was conducted on rather small samples...

..We tried to replicate these findings in a sample of 488 parent-proband trios recruited in Bulgaria. Probands had a diagnosis of schizophrenia (n = 441) or schizoaffective disorder (n = 47)...

..No copy number variations were found for any of the genes in any samples. Our data suggests that more reliable methods need to be used to validate the existence of CNVs before full scale association studies are carried out...

....

....

..Here, we consider the main points in study design, and illustrate the application of pooling using psychiatric phenotypes as an example...

....

..Our data provide complementary evidence for chromosome 8p as a susceptibility locus for schizophrenia, and suggest that genetic variation within this region may influence risk, at least in part, through effects on DTNBP1 expression...

..Further studies of dysbindin-1 and the proteins with which it interacts can be expected to throw light on the pathogenesis of schizophrenia...

....

..The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity...

..Sequencing of this region did not identify any evidence of a pathogenic exonic mutation. This suggests that the pathogenic change affects non-coding DNA and that the disease is caused by variation in gene or protein expression...

..We thus present a comprehensive resource for mutation detection screening of all HAS exons and/or linkage analysis of each HAS gene in a variety of disorders for which they are attractive candidates...

..Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained...

..Our assay conditions are generalisable, universal, robust and, therefore, for the first time, permit high-throughput association analysis at a realistic cost...

..The identification of mutations in these genes represents an important step forward in our understanding of the clinical, pathological, and genetic spectrum of ALS/FTLD diseases...

..This approach has the potential to provide a clarified picture of the majority of the genetic variation underlying disease pathogenesis...

....

..Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome-wide and at specific loci...

..If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small...

..There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations...

..Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles...