Showing papers by "Thordur Sigmundsson published in 1996"
University of Bonn1, University of Western Australia2, Western General Hospital3, University of Kiel4, King's College London5, Cardiff University6, Teikyo University7, Trinity College, Dublin8, Johns Hopkins University9, University of Geneva10, Seconda Università degli Studi di Napoli11, University of Pennsylvania12, Massachusetts Institute of Technology13, Rockefeller University14, Novartis15, Centre national de la recherche scientifique16, Virginia Commonwealth University17, Queen's University Belfast18, National Institutes of Health19, Imperial College London20, University of the Witwatersrand21, Stony Brook University22, Warneford Hospital23, University of Milan24, University College London25, University of Iceland26, Queen Mary University of London27, University of Utah28, Allegheny University of the Health Sciences29, University of Queensland30, QIMR Berghofer Medical Research Institute31, University of Iowa32, Icahn School of Medicine at Mount Sinai33, Columbia University34, Erasmus University Rotterdam35
TL;DR: Results are interpreted as inconclusive but suggestive of linkage in the latter two regions, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.
Abstract: In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = 0.001) and 2.68 (Combined sample, p = .0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p = .0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.
176 citations
TL;DR: The results do not support the hypothesis that GluR6 allelic variants provide a major gene contribution to the etiology of schizophrenia in a large proportion of these pedigrees.
Abstract: Objective : Previous research has consistently implicated genetic factors in the pathogenesis of schizophrenia. It has been hypothesized that an abnormality in glutamatergic function is of etiologic importance in schizophrenia, and therefore the glutamate receptor family of genes are potential susceptibility loci for schizophrenia. To test this hypothesis the authors sought to detect linkage between the GluR6 glutamate receptor gene and schizophrenia. Method : Twenty-three English and Icelandic families containing multiple cases of schizophrenia were genotyped with a microsatellite trinucleotide repeat polymorphism localized at the GluR6 glutamate receptor locus. Lod scores, model-free linkage analysis, and extended relative pair analysis were used to test for linkage. Results : No statistically significant evidence of linkage between GluR6 and schizophrenia was found. Conclusions : The results do not support the hypothesis that GluR6 allelic variants provide a major gene contribution to the etiology of schizophrenia in a large proportion of these pedigrees.
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