Failure to exclude a possible schizophrenia susceptibility locus on chromosome 13q14.1-q32 in Southern African Bantu-speaking families

Several recent reports have provided evidence suggesting linkage of markers on chromosome 13q14.1-q32 to schizophrenia in families from England, Wales, Japan and the USA, but not in Chinese families. We tested for linkage between markers in this region and schizophrenia in a sample of 16 families multiply affected with schizophrenia drawn from the Bantu-speaking black population of South Africa. Twelve markers spanning 76 cM of chromosome 13q were examined in these analyses, including 10 markers covering the most positive region in the studies of the English, Welsh and Chinese families, and two additional markers yielding the largest positive LOD scores in the American study. The map of markers used was D13S126-14.6 cM-D13S119-12.2 cM-D13S144-10.2 cM-D13S160-7.9 cM-D13S121-6.3 cM-D13S71-1.6 cM-D13S122- 4.9 cM-D13S128-8.9 cM-D13S770-1.4 cM-D13S779-2.2 cM-D13S64-7.4 cM-D13S173. Parametric two-point analysis yields strongly negative LOD scores across the region D13S71-D13S64 under all models, and D13S71-D13S173 under a recessive model, when analysing either the whole sample or affected individuals only. ALOD maxima are 0.0 when allowing for heterogeneity for all markers in this subset. Under recessive modelling, the ALOD maximum is 0.717, θ = 0.0, α = 0.45, for D13S126 when analysing all samples. Affected-only analysis of this marker yields a maximum LOD score of 0.645, θ = 0.1, and an ALOD maximum of 0.697, θ = 0.0, α = 0.55. Non-parametric multipoint analysis of these markers provides no support for excess sharing of alleles identical by descent, although D13S119 and D13S770 show some evidence for excess sharing of alleles identical by state.