Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families

Recent reports have strongly linked markers near the alpha-7 nicotinic chol inergic receptor subunit gene on human chromosome 15q13-q14 to a sensory ga ting deficit common in schizophrenics, and have shown positive though non-s ignificant results linking this region to the primary phenotype of schizoph renia in a sample of North American families. We therefore tested for linka ge between markers in this region of chromosome 15q and schizophrenia in a sample of 15 multiply affected and 5 single case families with schizophreni a drawn from the Bantu-speaking black population of South Africa. An initia l replication using markers from the original study gave an affected-only L OD score maximum of 1.08 under a recessive model at Theta=0.00 for D15S1360 , a dinucleotide polymorphism found on the same YAC as the alpha-7 receptor gene. Nonparametric affected-only multipoint analysis gave a Z-score of 1. 29, P=0.098, for D15S1360, and Z=1.45, p=0.075 for D15S118. We then increas ed the resolution of the map with an extended set of 20 markers. Again, two peaks were observed, with NPL scores of 1.81, p=0.037, at D15S1043 and 1.7 9 at D15S1360 and 1.80 at D15S1010, both p=0.037. Transmission disequilibri um testing of data from D15S1360 gave an allele-wise and genotype-wise chi( 2) of 6.59, 2 df, p=0.037. Haplotype transmission disequilibrium testing us ing a restricted allele and haplotype set from D15S1043 and D15S1360 gave a global chi(2) Of 10.647, 4 df, P=0.007, and a maximum chi(2) Of 6.567, 1 d f, P=0.004 for excess transmission of the 1.2 haplotype into affected offsp ring. (C) 2000 Wiley-Liss, Inc.