Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schizophrenia, a severe neuropsychiatric disorder, is believed to involve multiple genetic factors. A significant body of evidence supports a pivotal role for abnormalities of brain development in the disorder. Linkage signals for schizophrenia map to human chromosome 6q. To obtain a finer localization, we genotyped 180 single nucleotide polymorphisms (SNPs) in a young, inbred Arab-Israeli family sample with a limited number of founders. The SNPs were mostly within a approximately 7 Mb region around the strong linkage peak at 136.2 Mb that we had previously mapped. The most significant genetic association with schizophrenia for single SNPs and haplotypes was within a 500 kb genomic region of high linkage disequilibrium (LD) at 135.85 Mb. In a different, outbred, nuclear family sample that was not appropriate for linkage analysis, under-transmitted haplotypes incorporating the same SNPs (but not the individual SNPs) were significantly associated with schizophrenia. The implicated genomic region harbors the Abelson Helper Integration Site 1 (AHI1) gene, which showed the strongest association signal, and an adjacent, primate-specific gene, C6orf217. Mutations in human AHI1 underlie the autosomal recessive Joubert Syndrome with brain malformation and mental retardation. Previous comparative genomic analysis has suggested accelerated evolution of AHI1 in the human lineage. C6orf217 has multiple splice isoforms and is expressed in brain but does not seem to encode a functional protein. The two genes appear in opposite orientations and their regulatory upstream regions overlap, which might affect their expression. Both, AHI1 and C6orf217 appear to be highly relevant candidate genes for schizophrenia.
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PMID:AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia. 1677 25

The Abelson helper integration site 1 (AHI1) gene locus on chromosome 6q23 is among a group of candidate loci for schizophrenia susceptibility that were initially identified by linkage followed by linkage disequilibrium mapping, and subsequent replication of the association in an independent sample. Here, we present results of a replication study of AHI1 locus markers, previously implicated in schizophrenia, in a large European sample (in total 3907 affected and 7429 controls). Furthermore, we perform a meta-analysis of the implicated markers in 4496 affected and 18,920 controls. Both the replication study of new samples and the meta-analysis show evidence for significant overrepresentation of all tested alleles in patients compared with controls (meta-analysis; P = 8.2 x 10(-5)-1.7 x 10(-3), common OR = 1.09-1.11). The region contains two genes, AHI1 and C6orf217, and both genes-as well as the neighbouring phosphodiesterase 7B (PDE7B)-may be considered candidates for involvement in the genetic aetiology of schizophrenia.
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PMID:A large replication study and meta-analysis in European samples provides further support for association of AHI1 markers with schizophrenia. 2007 46

Association with schizophrenia of the Abelson Helper Integration Site 1 (AHI1) gene on chromosome 6q23 and the adjacent primate-specific gene, C6orf217, was demonstrated in an inbred, Arab Israeli family sample and replicated in an Icelandic case control sample. Further support was provided by a second replication in a large European sample and a meta-analysis that supported association with schizophrenia of all seven alleles overtransmitted to affected subjects in the original study. We examined constitutive expression of AHI1 and C6orf217 in immortalized lymphoblasts of patients from the Arab Israeli family sample in which the association with schizophrenia was originally discovered and population-matched normal controls, and in post-mortem brain of patients with schizophrenia and bipolar (BP) disorder and control subjects from the Stanley Medical Research Institute Collection. We found a significant effect of diagnostic group in the lymphoblast sample (F=5.72; df=2,39; p=0.006). Patients with early age of onset had higher AHI1 expression than controls and later onset patients (p=0.002; 0.03 respectively). C6orf217 expression in lymphoblasts was too low to measure. We found no difference in brain expression of AHI1 in schizophrenia or BP patients compared to controls. However, there was a genotypic difference in AHI1 expression for SNP rs9321501, which was strongly associated with schizophrenia in the original study. Genotypes that included the undertransmitted C allele (CC/AC) showed lower expression than the homozygous AA genotype (F=4.73, df=2,83; p=0.028). There was no significant difference in brain expression of C6orf217 between patients and controls and no genotypic effect. This study provides further evidence for involvement of AHI1 in susceptibility to schizophrenia.
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PMID:Lymphoblast and brain expression of AHI1 and the novel primate-specific gene, C6orf217, in schizophrenia and bipolar disorder. 2045 50