Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study

D.B. Wildenauer, S.G. Schwab, M. Albus, J. Hallmayer, B. Lerer, W. Maier, D. Blackwood, W. Muir, D. St.clair, S. Morris, H.W. Moises, L. Yang, H. Kristbjarnarson, T. Helgason, C. Wiese

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    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 40-52 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 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 = .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 hut 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.
    Original languageEnglish
    Pages (from-to)580-594
    JournalAmerican Journal of Medical Genetics Part A
    Volume67
    Publication statusPublished - 1996

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    Chromosomes, Human, Pair 8
    Chromosomes, Human, Pair 6
    Chromosomes, Human, Pair 3
    Pedigree
    Multicenter Studies
    Lod Score
    Schizophrenia
    Research
    Psychotic Disorders
    Microsatellite Repeats

    Cite this

    Wildenauer, D. B., Schwab, S. G., Albus, M., Hallmayer, J., Lerer, B., Maier, W., ... Wiese, C. (1996). Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study. American Journal of Medical Genetics Part A, 67, 580-594.
    Wildenauer, D.B. ; Schwab, S.G. ; Albus, M. ; Hallmayer, J. ; Lerer, B. ; Maier, W. ; Blackwood, D. ; Muir, W. ; St.clair, D. ; Morris, S. ; Moises, H.W. ; Yang, L. ; Kristbjarnarson, H. ; Helgason, T. ; Wiese, C. / Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study. In: American Journal of Medical Genetics Part A. 1996 ; Vol. 67. pp. 580-594.
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    title = "Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study",
    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 40-52 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 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 = .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 hut 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.",
    author = "D.B. Wildenauer and S.G. Schwab and M. Albus and J. Hallmayer and B. Lerer and W. Maier and D. Blackwood and W. Muir and D. St.clair and S. Morris and H.W. Moises and L. Yang and H. Kristbjarnarson and T. Helgason and C. Wiese",
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    Wildenauer, DB, Schwab, SG, Albus, M, Hallmayer, J, Lerer, B, Maier, W, Blackwood, D, Muir, W, St.clair, D, Morris, S, Moises, HW, Yang, L, Kristbjarnarson, H, Helgason, T & Wiese, C 1996, 'Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study' American Journal of Medical Genetics Part A, vol. 67, pp. 580-594.

    Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study. / Wildenauer, D.B.; Schwab, S.G.; Albus, M.; Hallmayer, J.; Lerer, B.; Maier, W.; Blackwood, D.; Muir, W.; St.clair, D.; Morris, S.; Moises, H.W.; Yang, L.; Kristbjarnarson, H.; Helgason, T.; Wiese, C.

    In: American Journal of Medical Genetics Part A, Vol. 67, 1996, p. 580-594.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study

    AU - Wildenauer, D.B.

    AU - Schwab, S.G.

    AU - Albus, M.

    AU - Hallmayer, J.

    AU - Lerer, B.

    AU - Maier, W.

    AU - Blackwood, D.

    AU - Muir, W.

    AU - St.clair, D.

    AU - Morris, S.

    AU - Moises, H.W.

    AU - Yang, L.

    AU - Kristbjarnarson, H.

    AU - Helgason, T.

    AU - Wiese, C.

    PY - 1996

    Y1 - 1996

    N2 - 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 40-52 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 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 = .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 hut 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.

    AB - 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 40-52 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 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 = .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 hut 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.

    M3 - Article

    VL - 67

    SP - 580

    EP - 594

    JO - Am J Med Genet A

    JF - Am J Med Genet A

    SN - 0148-7299

    ER -

    Wildenauer DB, Schwab SG, Albus M, Hallmayer J, Lerer B, Maier W et al. Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study. American Journal of Medical Genetics Part A. 1996;67:580-594.