47 A risk variant in another postsynaptic signaling molecule gene

47 A risk variant in another postsynaptic signaling molecule gene, AKT1, similarly showed interactions with COMT rs4680 genotype during working memory,32 with risk carriers for both genes showing especially inefficient lateral

prefrontal activation. While the papers reviewed above are limited to interactions between a maximum of four SNPs, the complexity of common genetic variation related to schizophrenia, which is likely to include effects of thousands of variants, will require a methodological effort to characterize interactions between larger sets of genes as they impact on imaging data. Calhoun and coworkers employed parallel independent component analysis, applied to auditory Inhibitors,research,lifescience,medical oddball task fMRI data, and extracted a set of 10 SNPs that were significantly related to imaging data and differed between a sample of patients and controls.48 While selection of SNPs and small sample size preclude conclusions about the specific genes they highlighted, Inhibitors,research,lifescience,medical their study provides proof of concept of the applicability of multivariate methods in imaging genetics. Copy number variants An important insight that has emerged from the last waves of genome -wide studies of schizophrenia concerns structural variations of the genome, where larger segments (up to several megabases) of genetic material are either Inhibitors,research,lifescience,medical duplicated

(microduplications) or missing (microdeletions).49,50 Convergent evidence now shows that such copy number variants (CNVs) are more common in schizophrenia than in the general population. In contrast to frequent genetic variants such as SNPs, the risk associated with some CNVs is much higher, and can correspond to a tenfold increase in disease risk. Inhibitors,research,lifescience,medical There is evidence that the presence of these variants is deleterious since they are under negative selection.51 Several specific regions now have strong evidence for conferring risk for schizophrenia, mapping on chromosome regions at 22q11, 15q13.3, 1q21.1, 15q11.2, 17p12, 2p16.3, 16p13.1, and Inhibitors,research,lifescience,medical 16p11.2. One of these, 22q11, has been known for a longer

time since this microdeletion causes a clinical syndrome (velocardiofacial, DiGeorge, or 22q11 deletion syndrome) that is recognizable by a pattern of somatic symptoms, such as heart defects or cleft palate, in addition to the Cilengitide increased risk for selleck chem Gefitinib psychosis.52 An important research frontier will be to understand, using imaging genetics, how these microdeletions impact on brain structure and function. This work is farthest in 22q11DS, which has been known for the SB1518 longest time. Here, convergent evidence implicates reductions in hippocampus and cerebellum, abnormal white matter connectivity, especially in the posterior corpus callosum, and reduced prefrontal activation (possibly compensated by parietal activation) during working memory tasks.

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