Genome-wide scan and schizophrenia in African Americans

Twelve families with multiple cases of schizophrenia, who were primarily of African American origin (43 affecteds in total) and were ascertained from probands from the Dallas/Fort Worth area, were subjected to a genome-wide linkage screen with polymorphic microsatellites. Parametric, nonparametric, and one-parameter multipoint analyses were performed using three diagnostic groups beginning with schizophrenia only (narrow dx), adding schizoaffective-depressed and cluster "A" personality disorders, and finally adding psychosis NOS (broad definition). For the parametric analysis, a dominant and recessive model previously described by Coon et al. was used. Regions providing most evidence for susceptibility loci were at 5p14.1-p13.1 and at 20q. At the 5p locus, a one-parameter multipoint lod score (Mlod) of 1.98 was obtained with D5S426, and 1.94 with D5S111, using the broad dx. A nonparametric linkage (NPL) score of 2.55 (P < 0.009) with D5S426 and of 2.49 (P = 0.008) (Z[lr] = 3.0) was found with D5S111. This replicates a previously described linkage seen in a large family from Puerto Rico. However, strongest evidence for linkage in our family set was seen in a region of chromosome 20 between D20S481 (at 93.9 cM) and 20qtr (nonparametric P = 0.00007 [Z(lr) = 8.2]). The genome-wide scan failed to replicate linkages to 3p26-p24, 6p24-p22, 8p22-p21, 10p, and 22q, described elsewhere. This suggests the possibility that predisposing loci in African Americans may be different from those described in Caucasians. An investigation of loci at 5p13.1-14.1 and 20qter is warranted in African Americans.