Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder.

摘要: In the search for biological causes of schizophrenia and bipolar disorder, glutamate neurotransmission has emerged as one a number candidate processes pathways where underlying gene deficits may be present. The analysis chromosomal rearrangements in individuals diagnosed with neuropsychiatric disorders is an established route to identification both Mendelian complex disorders. Here we describe set genes disrupted by, or proximal to, breakpoints (2p12, 2q31.3, 2q21.2, 11q23.3 11q24.2) patient chronic coexists mild learning disability (US: mental retardation). Of these genes, most promising member kainate-type ionotropic receptor family, GRIK4 (KA1). A subsequent systematic case-control association study on assessed its contribution psychiatric illness karyotypically normal population. This identified two discrete regions disease risk within locus: three single nucleotide polymorphism (SNP) markers corresponding haplotype associated susceptibility (P=0.0005, odds ratio (OR) 1.453, 95% CI 1.182-1.787) SNP protective effect against disorder (P=0.0002, OR 0.624, 0.485-0.802). After permutation correct multiple testing, haplotypes remained significant (P=0.0430, s.e. 0.0064 P=0.0190, 0.0043, respectively). We propose that convergent cytogenetic genetic findings provide molecular evidence common aetiologies different conditions further support 'glutamate hypothesis' psychotic illness.