Linkage analyses of schizophrenia to chromosome 6p24-p22: an attempt to replicate.

The present study evaluates evidence for linkage of schizophrenia to chromosome 6p24-p22. An independent sample of 211 families ascertained on the basis of having an affected sib-pair diagnosed with schizophrenia or schizoaffective disorder was assessed with seventeen polymorphic markers spanning a 37cM region. Linkage analysis was performed with parametric and non-parametric methods to test for cosegregation using 4 models of inheritance. Neither two-point nor multipoint non-parametric analyses reached significance at a level less than 0.01 for any markers examined in the region and lod score analyses were not suggestive of linkage. Based on initial findings in the present data set and recently published linkage results, two specific areas were densely covered with markers and tested for linkage disequilibrium. After correcting for multiple comparisons within each locus, no significant deviation from expected allele transmission ratios was observed. The present findings together with the published literature fail to find consistent evidence of a linkage for schizophrenia to a single locus on chromosome 6.

[1]  H. Kunugi,et al.  An overview of schizophrenia genetic research presented at the 1995 World Congress on Psychiatric Genetics, Cardiff , 1996, Schizophrenia Research.

[2]  B. Korf,et al.  Neurobehavioral profiles of children with neurofibromatosis 1 referred for learning disabilities are sex-specific. , 1996, American journal of medical genetics.

[3]  R. Straub,et al.  Reflections on the evidence for a vulnerability locus for schizophrenia on chromosome 6p24-22. , 1996, American journal of medical genetics.

[4]  J. Weissenbach,et al.  An international two–stage genome–wide search for schizophrenia susceptibility genes , 1995, Nature Genetics.

[5]  Melanie C. Green,et al.  Schizophrenia susceptibility and chromosome 6p24–22 , 1995, Nature Genetics.

[6]  Margot Albus,et al.  Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib–pair linkage analysis , 1995, Nature Genetics.

[7]  J. Ott,et al.  Schizophrenia susceptibility and chromosome 6p24–22 , 1995, Nature Genetics.

[8]  L. Siever,et al.  Schizophrenia susceptibility and chromosome 6p24–22 , 1995, Nature Genetics.

[9]  R. Straub,et al.  A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity , 1995, Nature Genetics.

[10]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[11]  K. Kendler,et al.  Examining the validity of DSM-III-R schizoaffective disorder and its putative subtypes in the Roscommon Family Study. , 1995, The American journal of psychiatry.

[12]  J. Ziegle,et al.  Evidence for a susceptibility locus for schizophrenia on chromosome 6pter–p22 , 1995, Nature Genetics.

[13]  J. Nurnberger,et al.  Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. , 1994, Archives of general psychiatry.

[14]  J. Weissenbach,et al.  A method for constructing radiation hybrid maps of whole genomes , 1994, Nature Genetics.

[15]  A. C. Chinault,et al.  Mapping and cloning of the critical region for the spinocerebellar ataxia type 1 gene (SCA1) in a yeast artificial chromosome contig spanning 1.2 Mb. , 1993, Genomics.

[16]  A A Schäffer,et al.  Faster sequential genetic linkage computations. , 1993, American journal of human genetics.

[17]  G. Gyapay,et al.  A second-generation linkage map of the human genome , 1992, Nature.

[18]  R. Myers,et al.  Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. , 1990, Science.

[19]  J. Ott Analysis of Human Genetic Linkage , 1985 .

[20]  R. Elston,et al.  The investigation of linkage between a quantitative trait and a marker locus , 1972, Behavior genetics.