No evidence for linkage of the CHRNA7 gene region in Canadian schizophrenia families.

Abstract

Schizophrenia patients demonstrate a deficiency in the filtering of sensory information, and one specific measure involves a response to the second of a pair of auditory stimuli. A neurophysiological measure of this consists of the electroencephalographic response to pairs of auditory signals, emitted fractions of a second apart. Schizophrenic patients and some of their unaffected relatives show a failure of inhibition of a second tone if it occurs 50 msec after the first. A recent genome scan indicated that the gating defect is linked to the alpha 7 neuronal nicotinic acetyl choline receptor gene on chromosome 15. We genotyped 5 schizophrenia families with a total of 96 subjects with a dinucleotide polymorphic marker located less than 120 kb from the first exon of the alpha 7 neuronal nicotinic acetylcholine receptor gene. Linkage analysis was undertaken using parametric and nonparametric statistical methods. The results of the parametric analysis showed negative lod scores under both narrow and broad diagnosis (lod = -3.6 and -4.8, respectively, at theta = 0), and dominant and recessive modes of transmission of the disease. Nonparametric analysis using GENEHUNTER produced nonsignificant NPL scores (NPL = -0.4 and -0.3 for broad and narrow diagnoses, respectively). In summary, we did not find any evidence that the alpha 7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is linked to schizophrenia. However, we have not been able to assess the P50 measures in these families.