NO EVIDENCE FOR LINKAGE OF THE CHRNA7 GENE REGION IN CANADIAN SCHIZOPHRENIA FAMILIES

Schizophrenia patients demonstrate a deficiency in the filtering of se nsory 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 aud itory signals, emitted fractions of a second apart. Schizophrenic pati ents and some of their unaffected relatives show a failure of inhibiti on of a second tone if it occurs 50 msec after the first. A recent gen ome scan indicated that the gating defect is linked to the alpha 7 neu ronal nicotinic acetyl choline receptor gene on chromosome 15, We geno typed 5 schizophrenia families with a total of 96 subjects with a dinu cleotide polymorphic marker located less than 120 kb from the first ex on of the alpha 7 neuronal nicotinic acetylcholine receptor gene. Link age analysis was undertaken using parametric and nonparametric statist ical methods. The results of the parametric analysis showed negative l od scores under both narrow and broad diagnosis (lod = -3.6 and -4,8, respectively, at theta = 0), and dominant and recessive modes of trans mission of the disease. Nonparametric analysis using GENEHUNTER produc ed nonsignificant NPL scores (NPL = -0.4 and -0.3 for broad and narrow diagnoses, respectively). In summary, we did not find any evidence th at 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. (C) 1998 Wiley-Liss, Inc.