Although GWASs of bipolar disorder have identified a number of potentially relevant genetic variants, the widely acknowledged formal threshold for genome-wide significance of P=5 x 10-8 has only been surpassed so far for variation in ANK3. Table II Published genome-wide association studies (GWASs) for bipolar disorder.34-39 The number of variants investigated, the best associated singlenucleotide polymorphism(s)-SNP(s) – found and the gene(s) containing that SNP(s), the corresponding Pvalue(s), … Future studies involving larger samples, the pooling of datasets, and higher statistical power are expected to identify additional specific risk factors for bipolar disorder and
Inhibitors,research,lifescience,medical schizophrenia. Copy number variations
Small chromosomal aberrations (microdeletions and microduplications, Inhibitors,research,lifescience,medical collectively known as copy number variations, CNV) may confer a risk for schizophrenia, as illustrated by the 22q11.2 deletion syndrome (22q11.2DS). This is a common microdeletion syndrome with congenital and late-onset features. Patients have a high risk for neuropsychiatric diseases including psychotic disorders and major depression.42-44 It has not been possible to correlate the extent of the deletion with the occurrence of schizophrenia in these patients, and there Inhibitors,research,lifescience,medical is experimental evidence that increased susceptibility may require the altered expression of several genes within the 22q11.2 region.45-46 This may explain why no replicable results have been obtained from attempts to implicate individual genes within the deletion region as susceptibility genes for schizophrenia.47 Schizophrenia The application Inhibitors,research,lifescience,medical of new technologies such as comparative genomic hybridization (CGH) and SNP arrays in GWASs has enabled the BMS-387032 order identification of small chromosomal aberrations on a genome-wide scale. Initial studies reported an increased Inhibitors,research,lifescience,medical rate of aberrations in schizophrenia48,49 and subsequent studies have implicated specific chromosomal regions.28,50-54 Implicated L-NAME HCl aberrations
include microdeletions in chromosomal regions 1q21.1, 2p16.3, 15q11.2, and 15q13.3, as well as microduplications in chromosomal regions 15q13.1 and 16p11.2. Although all of these variants are observed more frequently in patients than in controls (with odds ratios of >10 for some variants), the frequency of each individual variant in schizophrenia patients is low (<1%). Further studies are required to determine the penetrance and mutation rate of these aberrations, as well as their phenotypic spectrum. Research has shown that some variants also occur more frequently in patients with other central nervous system phenotypes such as autism, mental disability, and epilepsy.55-58 The mechanisms that underlie the phenotypic outcome however, remain unknown.