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

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Abstract
Recent reports have strongly linked markers near the α‐7 nicotinic cholinergic receptor subunit gene on human chromosome 15q13‐q14 to a sensory gating deficit common in schizophrenics, and have shown positive though non‐significant results linking this region to the primary phenotype of schizophrenia in a sample of North American families. We therefore tested for linkage between markers in this region of chromosome 15q and schizophrenia in a sample of 15 multiply affected and 5 single case families with schizophrenia drawn from the Bantu‐speaking black population of South Africa. An initial replication using markers from the original study gave an affected‐only LOD score maximum of 1.08 under a recessive model at Θ=0.00 for D15S1360, a dinucleotide polymorphism found on the same YAC as the α‐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 increased 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 1.79 at D15S1360 and 1.80 at D15S1010, both p=0.037. Transmission disequilibrium testing of data from D15S1360 gave an allele‐wise and genotype‐wise χ2 of 6.59, 2 df, p=0.037. Haplotype transmission disequilibrium testing using a restricted allele and haplotype set from D15S1043 and D15S1360 gave a global χ2 of 10.647, 4 df, P=0.007, and a maximum χ2 of 6.567, 1 df, P=0.004 for excess transmission of the 1.2 haplotype into affected offspring. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:196–201, 2000.

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