Multiple genes in the 15q13-q14 chromosomal region are associated with schizophrenia

Abstract

Objective The chromosomal region, 15q13-q14, including the α7 nicotinic acetylcholine receptor gene, CHRNA7, is a replicated region for schizophrenia. This study fine-mapped genes at 15q13-q14 to determine whether the association is unique to CHRNA7. Methods Family-based and case–control association studies were performed on Caucasian-non-Hispanic and African-American individuals from 120 families as well as 468 individual patients with schizophrenia and 144 well-characterized controls. Single-nucleotide polymorphism (SNP) markers were genotyped, and association analyses carried out for the outcomes of schizophrenia, smoking, and smoking in schizophrenia. Results Three genes were associated with schizophrenia in both ethnic populations: TRPM1, KLF13, and RYR3. Two SNPs in CHRNA7 were associated with schizophrenia in African-Americans, and a second SNP in CHRNA7 was significant for an association with smoking and smoking in schizophrenia in Caucasians. Conclusion Results of these studies support association of the 15q13-q14 region with schizophrenia. The broad positive association suggests that more than one 15q gene may be contributing to the disorder, either in combination or through a regulatory mechanism. Psychiatr Genet 22:1–14 © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

“…A significant association of SNP rs8028396 with smoking, as well as with smoking in schizophrenia, in a non-Hispanic Caucasian population was observed (Stephens et al, 2012;Neri et al, 2012). SNP rs3087454 was first shown to be significantly associated to schizophrenia (Stephens et al, 2009) and also influenced differences in synaptic activity, as detected by functional magnetic resonance imaging, between patients with schizophrenia and control subjects performing an auditory oddball task (Tregellas et al, 2010).…”

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

“…Exons A, B, C, and E are copies of ULK4 exons (yellow). Exons D, F, and G (green) share homology with the GOLGA8B gene, 2.5 Mb 3′ of CHRNA7 (Stephens et al, 2012). Exons A-F constitute the genetic element FAM7A, which is duplicated at least four times on chromosome 15q13.3, FAM7A(1-4)(Figure 1A).…”

Electrophysiological Endophenotypes in Rodent Models of Schizophrenia and Psychosis

“…The deletion comprises six genes including two genes for receptors, TRPM1 and CHRNA7 (37), and has been functionally implicated in the expression of inhibitory markers (38). A mouse model of this mutation recapitulates abnormalities in oscillatory and evoked activity seen in EEG studies of SCZ patients.…”