Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families

Abstract

Eight Utah multigenerational families, each with three to six cases of schizophrenia, were phenotyped with two specific measures of inhibitory neurophysiological functioning, P50 auditory sensory gating (P50), and antisaccade ocular motor performance (AS). A genomewide linkage analysis was performed to screen for loci underlying a qualitative phenotype combining the P50 and AS measures. For this composite inhibitory phenotype, the strongest evidence for linkage was to the D22s315 marker on chromosome 22q (lod score = 3.55, theta = 0) under an autosomal dominant model. Simulation analyses indicate that this 3.55 lod score is unlikely to represent a false positive result. Lod scores were 2.0 or greater for markers flanking D22s315. A nonparametric linkage (NPL) analysis of the chromosome 22 data showed evidence for allele sharing over the broad region surrounding D22s315 with a maximum NPL score of 3.83 (p = .002) for all pedigrees combined.