Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib–pair linkage analysis

Abstract

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies1–3, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci4. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occuring near D6S274, located in 6p22. However, we obtained a lod score of −2 at D6S296, the locus found by others to provide the greatest linkage evidence5. At D6S274, we report a positive lod score as do Straub et al.5 (individually non-significant). A combined total lod of 3.6–4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.

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References

  1. 1

    Bertelsen, A. Controversies and consistencies in psychiatric genetics. Acta Psychiat. Scand. 71, 61–75 (1985).

  2. 2

    Kendler, K.S. Familial aggregation of schizophrenia and schizophrenia spectrum disorders. Arch. gen. Psychiat. 45, 377–383 (1988).

  3. 3

    Gottesmann, I.I. & Bertelsen, A. Confirming unexpressed genotypes for schizophrenia: risks in the offspring of Fischers identical and fraternal discordant twins. Arch. gen. Psychiat. 46, 867–872 (1989).

  4. 4

    Risch, N. Linkage strategies for genetically complex traits. I. multilocus models. Am. J. hum. Genet. 46, 229–241 (1990).

  5. 5

    Straub, R. et al. A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity. Nature Genet. 11, 287–293 (1995).

  6. 6

    Gyapay, G. et al. The 1993–94 Généthon human genetic linkage map. Nature Genet. 7, 246–339 (1994).

  7. 7

    Risch, N. Linkage strategies for genetically complex traits. II. the power of affected relative pairs. Am. J. hum. Genet. 46, 229–241 (1990).

  8. 8

    Risch, N. Exclusion mapping for complex diseases. Am. J. hum. Genet. 53, A185 (1993).

  9. 9

    Maier, W. et al. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch. gen. Psychiat. 50, 871–883 (1993).

  10. 10

    Penrose, L.S. The general purpose sib-pair linkage test. Ann. Eugen. 18, 120–124 (1953).

  11. 11

    Suarez, B.K. & Van Erdewegh, P. A comparison of three affected-sib-pair scoring method to detect HLA-linked disease susceptibility genes. Am. J. med. Genet. 18, 135–146 (1984).

  12. 12

    Knapp, M., Seuchter, S.A. & Baur, M.P. Linkage analysis in nuclear families, 1: Optimality criteria for affected sib-pair tests. Hum. Hered. 44, 37–43 (1994).

  13. 13

    Knapp, M., Seuchter, S.A. & Baur, M.R. Linkage analysis in nuclear families, 2: relationship between affected sib-pair tests and lod score analysis. Hum. Hered. 44, 44–51 (1994).

  14. 14

    Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am. J. hum. Genet. 37, 482–498 (1985).

  15. 15

    Polymeropoulos, M.H., Rath, D.S., Xiao, H. & Merril, T.R. Tetranucleotide repeat polymorphism at the human coagulation factor XIIIA subunit gene (F13A1). Nucl. Acids Res. 19, 4306 (1991).

  16. 16

    Macaubas, C., Hallmayer, J., Kalil, J., Grumet, C. & Mignot, E. Extensive polymorphism of a (CA)n microsatellite located in the HLA-DQA1/DQB1 class II region. Hum. Immunol. 42, 209–220 (1995).

  17. 17

    Wang, S. et al. Evidence for a susceptibility locus for schizophrenia on chromosome 6pter–p22. Nature Genet. 10, 41–46 (1995).

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