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

Riley, Brien P.; Lin, Margaret J.; Mogudi-Carter, M.; Jenkins, Trefor; Williamson, Robert; Powell, John; Collier, David; Murray, Robin M.

doi:10.1097/00041444-199800830-00004

Cited by 13 publications

(11 citation statements)

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“…In the 166 schizophrenia families collected by the Veterans Affairs Cooperative Linkage Study of Schizophrenia, Faraone et al [2002] reported a peak LOD score of 1.43 between markers D13S1241 and D13S159. Although there are some negative reports [Coon et al, 1994;Faraone et al, 1998;Kaufmann et al, 1998;Riley et al, 1998;DeLisi et al, 2000;Levinson et al, 2000;Mowry et al, 2000;Schwab et al, 2000;Gurling et al, 2001], it is notable that the peak LOD scores reported by the positive studies cluster in a region ranging from 65 to 95 cM. For the present analyses, our peak LOD score was nearby at 107 cM.…”

Section: Results Of Genome Scanmentioning

confidence: 39%

A Novel Permutation Testing Method Implicates Sixteen Nicotinic Acetylcholine Receptor Genes as Risk Factors for Smoking in Schizophrenia Families

Faraone

Taylor

et al. 2004

Hum Hered

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Smoking is a common correlate of schizophrenia, which leads to medical morbidity. Although twin and adoption studies have consistently implicated genes in the etiology of both smoking and schizophrenia, finding genes has been difficult. Several authors have suggested that clinical or neurobiological features associated with schizophrenia, such as smoking, might improve the ability to detect schizophrenia susceptibility genes by identifying genes related to the etiology of that feature. The objective of this study is to assess evidence for linkage of sixteen nicotinic acetylcholine receptor genes and smoking in schizophrenia families, using data from the NIMH Genetics Initiative for schizophrenia. Sixteen nicotinic acetylcholine receptor genes were selected prior to analysis. We used a multipoint sibling pair linkage analysis program, SIBPAL2, with a smoking trait in schizophrenia families. The significance of the group of candidate genes, in addition to each individual candidate gene, was assessed using permutation testing, which adjusted for multiple comparisons. The group of genes showed significant linkage to the smoking trait after adjusting for multiple comparisons through permutation testing (p = 0.039). In addition, two of the individual candidate genes were significant (CHRNA2, p = 0.044) and (CHRNB2, p = 0.015) and two genes were marginally significant (CHRNA7, p = 0.095; CHRNA1, p = 0.076). The significance of the complex hypothesis, involving sixteen genes, implicates the nicotinic system in smoking for schizophrenic families. Individual gene analysis suggests that CHRNA2 and CHRNB2 may play a particular role in this involvement. Such findings help prioritize genes for future case control studies. In addition, we provide a novel permutation method that is useful in future analyses involving a single hypothesis, with multiple candidate genes.

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Section: Results Of Genome Scanmentioning

confidence: 39%

A Novel Permutation Testing Method Implicates Sixteen Nicotinic Acetylcholine Receptor Genes as Risk Factors for Smoking in Schizophrenia Families

Faraone

Taylor

et al. 2004

Hum Hered

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“…Data from other genome screens and replication studies gave mixed results. Analyses of 15 South African Bantu families gave small positive LOD and NPLZ scores across the region examined by Lin et al [Riley et al, 1998]. Data from 275 of the ISHDSF families gave a LOD of 1.36 under a recessive model at D13S779 close to the positive region reported by Lin et al, but nonsignificant NPLZ results across the region [Straub et al, 1997a].…”

Section: Article American Journal Of Medical Genetics (Semin Med Gementioning

confidence: 86%

Linkage and associated studies of schizophrenia

2000

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Genetic epidemiology has provided consistent evidence over many years that schizophrenia has a genetic component, and that this genetic component is complex, polygenic, and involves epistatic interaction between loci. Molecular genetics studies have, however, so far failed to identify any DNA variant that can be demonstrated to contribute to either liability to schizophrenia or to any identifiable part of the underlying pathology. Replication studies of positive findings have been difficult to interpret for a variety of reasons. First, few have reproduced the initial findings, which may be due either to random variation between two samples in the genetic inputs involved, or to a lack of power to replicate an effect at a given alpha level. Where positive data have been found in replication studies, the positioning of the locus has been unreliable, leading no closer to positional cloning of genes involved. However, an assessment of all the linkage studies performed over the past ten years does suggest a number of regions where positive results are found numerous times. These include regions on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 18, 22 and the X. All of these data are critically reviewed and their locations compared. Reasons for the difficulty in obtaining consistent results and possible strategies for overcoming them are discussed. Am. J. Med. Genet. (Semin. Med. Genet.) 97:23-44, 2000.

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“…These families have been described in detail elsewhere (Riley et al, 1996a;Riley et al, 1996b;Riley et al, 1997;Riley et al, 1998). Microsatellite markers were amplified using standard PCR conditions and publicly available primer sequences.…”

Section: Methodsmentioning

confidence: 99%

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

Riley¹,

Makoff²,

Mogudi-Carter

et al. 2000

Am. J. Med. Genet.

114

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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.

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

Cited by 13 publications

References 0 publications

A Novel Permutation Testing Method Implicates Sixteen Nicotinic Acetylcholine Receptor Genes as Risk Factors for Smoking in Schizophrenia Families

A Novel Permutation Testing Method Implicates Sixteen Nicotinic Acetylcholine Receptor Genes as Risk Factors for Smoking in Schizophrenia Families

Linkage and associated studies of schizophrenia

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

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