Skip to main content
SpringerLink
Log in

The genetic epidemiology of schizophrenia and the design of linkage studies

  • Molecular Genetics of Schizophrenia
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Summary

There are three aspects of schizophrenia that are challenges to the design of linkage studies. First, analysis of twin and family data have consistently failed to identify a single major gene effect. Second, ascertainment of multiplex families does not guarantee the sampling of families in whom a major gene is segregating even if such a gene exists. Third, environmental influences appear to play an essential role in the etiology of at least some schizophrenia. The implications of these features for linkage strategies in schizophrenia are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baron M (1986) Genetics of schizophrenia: I. Familial patterns and mode of inheritance. Biol Psychiatry 21:1051–1066

    Google Scholar 

  • Böök JA (1953) A genetic and neuropsychiatric investigation of a North Swedish population. Acta Genet Stat Med (Basel) 4:1–100

    Google Scholar 

  • Carter CL, Chung CS (1980) Segregation analysis of schizophrenia under a mixed model. Hum Hered 30:350–356

    Google Scholar 

  • Davison K (1987) Organic and toxic concomitents of schizophrenia: association or chance? In: Helmchen H, Henn FA (eds) Biological perspectives of schizophrenia Wiley, New York, pp 139–160

    Google Scholar 

  • Eaton WW (1985) Epidemiology of schizophrenia. Epidemiol Rev 7:105–126

    Google Scholar 

  • Eaves LJ, Kendler KS, Schulz SC (1986) The familial sporadic classification: its power for the resolution of genetic and environmental etiologic factors. J Psychiatry Res 20:115–130

    Google Scholar 

  • Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE (1987) Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 325:783–787

    Google Scholar 

  • Elston RC, Campbell MA (1970) Schizophrenia: evidence for a major gene hypothesis. Behav Genet 1:3–10

    Google Scholar 

  • Elston RC, Namboodiri KK, Spence MA, Rainer JD (1978) A genetic study of schizophrenia pedigrees: II. One-locus hypotheses. Neuropsychobiology 4:193–206

    Google Scholar 

  • Erlenmeyer-Kimling L (1978) Fertility of psychotics: demography. In: Cancro R (ed) Annual review of the schizophrenic syndrome, vol 5. Brunner Mazel, New York, pp 298:333

    Google Scholar 

  • Essen-Moller E, Larson H, Uddenberg CE, White G (1956) Individual traits and morbidity in a Swedish rural population. Acta Psychiatr Neurol Scand Suppl 100

  • Falconer DS (1965) The inheritance of liability to certain diseases estimated from the incidence among relatives. Ann Hum Genet 29:51–76

    Google Scholar 

  • Faraone SV, Tsuang MT (1985) Quantitative models of the genetic transmission of schizophrenia. Psychol Bull 98:41–66

    Google Scholar 

  • Gottesman II, Bertelsen A (1989) Confirming unexpressed genotypes for schizophrenia: risks in the offspring of Fischer's Danish identical and fraternal discordant twins. Arch Gen Psychiatry 46:867–872

    Google Scholar 

  • Gottesman II, McGue G (1990) Mixed and mixed-up models for the transmission of schizophrenia. In: Cichetti D, Grove WM (eds) Thinking clearly about psychology: essays in honor of Paul E. Meehl. Volume II: Essays on Individual Differences. University of Minnesota Press, Minneapolis

    Google Scholar 

  • Gottesman II, Shields J (1967) A polygenic theory of schizophrenia. Proc Natl Acad Sci USA 58:199–205

    Google Scholar 

  • Gottesman II, Shields J, Hanson DR (1982) Schizophrenia: the epigenetic puzzle. Cambridge University Press, Cambridge

    Google Scholar 

  • Heston LL (1970) The genetics of schizophrenia and schizoid disease. Science 167:249–256

    Google Scholar 

  • James JW (1971) Frequency in relatives for an all-or-none trait. Ann Hum Genet 35:47–49

    Google Scholar 

  • Kidd KK, Cavalli-Sforza LL (1973) An analysis of the genetics of schizophrenia. Soc Biol 20:254–265

    Google Scholar 

  • Lindelius R (1970) A study of schizophrenia: a clinical, prognostic, and family investigation. Acta Psychiatr Scand Suppl 216

  • Matthysse SW, Holzman PS, Lange K (1986) The genetic transmission of schizophrenia: application of Mendelian latent structure analysis to eye tracking dysfunctions in schizophrenia and affective disorder. J Psychiatr Res 20:57–65

    Google Scholar 

  • McGue M, Gottesman II, Rao DC (1983) The transmission of schizophrenia under a multifactorial threshold model. Am J Hum Genet 35:1161–1178

    Google Scholar 

  • McGue M, Gottesman II, Rao DC (1985) Resolving genetic models for the transmission of schizophrenia. Genet Epidemiol 2:99–110

    Google Scholar 

  • McGue M, Gottesman II, Rao DC (1986) The analysis of schizophrenia family data. Behav Genet 16:75–87

    Google Scholar 

  • Meehl PE (1972a) A critical afterword. In: Gottesman II Shields J (eds) Schizophrenia and genetics. A twin study vantage point. Academic Press, New York, pp 367–415

    Google Scholar 

  • Meehl PE (1972b) Specific genetic etiology, psychodynamics, and therapeutic nihilism. Int J Ment Health 1:10–27

    Google Scholar 

  • Morton NE, MacLean CJ (1974) Analysis of family resemblance: III. Complex segregation analysis of quantitative traits. Am J Hum Genet 26:489–503

    Google Scholar 

  • Ødegaard Ø (1980) Fertility of psychiatric first admissions in Norway 1936–1975. Acta Psychiatr Scand 62:212–220

    Google Scholar 

  • O'Rourke DH, Gottesman II, Suarez BK, Rice J, Reich T (1982) Refutation of the general single-locus model for the etiology of schizophrenia. Am J Hum Genet 34:630–649

    Google Scholar 

  • Rao DC, Morton NE, Gottesman II, Lew R (1981) Path analysis of qualitative data on pairs of relatives: application to schizophrenia. Hum Hered 33:325–333

    Google Scholar 

  • Risch N, Baron M (1984) Segragation analysis of schizophrenia and related disorders. Am J Hum Genet 36:1039–1059

    Google Scholar 

  • Rosanoff AJ, Orr FI (1911) A study in insanity in the light of the Mendelian theory. Am J Insanity 68:221–261

    Google Scholar 

  • Rosenthal D (1972) Three adoption studies of heredity in the schizophrenic disorders. Int J Ment Health, 1:63–75

    Google Scholar 

  • Rüdin E (1916) Zur Vererbung und Neuentstehung der Dementia Praecox. Springer, Berlin

    Google Scholar 

  • Sherrington R, Brynjolfsson J, Petursson H, Potter M, Dudleston K, Barraclough B, Wasmuth J, Dobbs M, Gurling H (1988) Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 326:164–167

    Google Scholar 

  • Slater E (1958) The monogenic theory of schizophrenia. Acta Genet Stat Med (Basel) 8:50–56

    Google Scholar 

  • Slater E, Cowie V (1971) The genetics of mental disorders. Oxford Press, London

    Google Scholar 

  • Smith SD, Kimberling WJ, Pennington BF, Lubs HA (1983) Specific reading disability: identification of an inherited form through linkage analysis. Science 219:1345–1347

    Google Scholar 

  • St. George-Hyslop PH, Tanzi RE, Polinsky RJ, Haines JL, Nee L, Watkins PC, Myers RH, Feldman RG, Pollen D, Drachman D, Growdon J, Bruni A, Foncin JF, Salmon D, Frommelt P, Amaducci L, Sorbi S, Piacentini S, Stewart GD, Hobbs WJ, Conneally PM, Gusella JF (1987) The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science 235:885–890

    Google Scholar 

  • Thoday JM (1967) New insights into continuous variation. In: Crow JF, Neel JV (eds) Proceedings of the Third International Congress of Human Genetics, Johns Hopkins Press, Baltimore, pp 339–350

    Google Scholar 

  • Tsuang MT, Bucher KD, Fleming JA (1982) Testing the monogenetic theory of schizophrenia: an application of segregation analysis to blind family data. Br J Psychiatry 140:595–599

    Google Scholar 

  • Vogel F, Motulsky AG (1986) Human genetics: problems and approaches. Springer, New York Berlin Heidelberg

    Google Scholar 

  • Vogel HP (1979) Fertility and sibship size in a psychiatric patient population: a national comparison with census data. Acta Psychiatr Scand 60:483–503

    Google Scholar 

  • Vogler GP, Gottesman II, McGue MK, Rao DC (1990) Mixed model segregation analysis in the Lindelius Swedish pedigrees. Behav Genetic 20:461–472

    Google Scholar 

  • Wright S (1934) An analysis of variability in number of digits in an inbred strain of guinea pigs. Genetics 19:506–536

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology and Genetics, University of Minnesota, Minneapolis, USA

    M. McGue

  2. Department of Psychology, University of Virginia, USA

    I. I. Gottesman

Authors
  1. M. McGue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. I. Gottesman
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

A previous version of this paper was published in Schizophrenia Bulletin (1989, 15:453–464) and reprinted in V. Bulyzhenkov, Y. Chirsten, L. Prilipko (eds) (1990) Genetic approaches in the prevention of mental disorders, Berlin: Springer-Verlag, pp 24–38

Rights and permissions

Reprints and permissions

About this article

Cite this article

McGue, M., Gottesman, I.I. The genetic epidemiology of schizophrenia and the design of linkage studies. Eur Arch Psychiatry Clin Nuerosci 240, 174–181 (1991). https://doi.org/10.1007/BF02190760

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02190760

Key words

Search

Navigation