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Further investigation of a chromosome 15 locus in schizophrenia: Analysis of affected sibpairs from the NIMH genetics initiative
Authors:Sherry Leonard  Judith Gault  Theodore Moore  Jan Hopkins  Misi Robinson  Ann Olincy  Lawrence E. Adler  C. Robert Cloninger  Charles A. Kaufmann  Ming T. Tsuang  Stephen V. Faraone  Dolores Malaspina  Dragan M. Svrakic  Robert Freedman
Affiliation:Departments of Psychiatry and Pharmacology, University of Colorado Health Sciences Center and Denver VA Medical Center, Denver, Colorado
Abstract:
Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the α7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:308–312, 1998. © 1998 Wiley-Liss, Inc.
Keywords:human chromosome pair 15  genetic linkage  nicotinic receptor  polymorphism  auditory evoked potential
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