SUPPORT FOR A POSSIBLE SCHIZOPHRENIA VULNERABILITY LOCUS IN REGION 5Q22-31 IN IRISH FAMILIES

In our genome scan for schizophrenia genes in 265 Irish pedigrees, mar ker D5S818 in 5q22 produced the second best result of the first 223 ma rkers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizo phrenia in region 5q22-31. This region appears to be distinct from tho se chromosome 5 regions studied in two prior reports,(1,2) but the sam e as that producing positive results in the report by Wildenauer and c olleagues(3) found elsewhere in this issue. The largest pairwise heter ogeneity LOD (H-LOD) score was found with marker D5S393 (max 3.04, P = 0.0005), assuming a narrow phenotypic category, and a genetic model w ith intermediate heterozygotic liability. In marked contrast to the H- LOD scores from our sample with markers from the regions of interest o n chromosomes 6p(4) and 8p, expanding the disease definition to includ e schizophrenia spectrum or nonspectrum disorders produced substantial ly smaller scores, with a number of markers failing to yield positive values at any recombination fraction, Using multipoint H-LODS, the str ongest evidence for linkage occurs under the narrow phenotypic definit ion and recessive genetic model, with a peak at marker D5S804 (max 3.3 5, P = 0.0002). Multipoint nonparametric linkage analysis produced a p eak in the same location (max z = 2.84, P = 0.002) with the narrow phe notypic definition. This putative vulnerability locus appears to be se gregating in 10-25% of the families studied, but this estimate is tent ative. Comparison of individual family multipoint H-LOD scores at the regions of interest on chromosomes 6p, 8p and 5q showed that only a mi nority of families yield high lod scores in two or three regions.