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 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 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 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 chi(2) 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 chi(2) of 10.647, 4 df, P=0.007, and a maximum chi(2) 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.
Riley
B P
BP
Departments of Psychological Medicine and Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. B.Riley@iop.kcl.ac.uk
Makoff
A
A
Mogudi-Carter
M
M
Jenkins
T
T
Williamson
R
R
Collier
D
D
Murray
R
R
D002038:Bungarotoxins / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D018562:Disease Transmission, Infectious; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D018709:Statistics, Nonparametric; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579167:Chrna7 protein, human; D005819:Genetic Markers; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor