A SCHIZOPHRENIA LOCUS MAY BE LOCATED IN REGION 10P15-P11

In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability g enes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22- p21, Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. W e then tested a total of 12 markers across a reagion of 32 centimorgan s in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model, The largest pairwise H-LOD score was found w ith marker D10S2443 (maximum 1.95, P = 0.005), Using multipoint H-LODs , we found a broad peak (maximum 1.91, P = 0.006) extending over the 1 1 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonp arametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1,88, P = 0,03 ), Based on estimates from the multipoint analysis, this putative vuln erability locus appears to be segregating in 5-15% of the families stu died, but this estimate should be viewed with caution. When evaluated in the context of our genome scan resuits, the evidence suggests the p ossibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11. Am. J, Med, Genet, (Neuropsychiat r, Genet.) 81:296-301, 1998, (C) 1998 Wiley-Liss, Inc.