Skip to main content
SpringerLink
Log in

Genetic Linkage in Schizophrenia: Perspectives from Genetic Epidemiology

  • Conference paper
Genetic Approaches in the Prevention of Mental Disorders

  • 48 Accesses

Summary

Research on the genetic epidemiology of schizophrenia is briefly and selectively reviewed. Three salient features of schizophrenia that represent challenges to the design of linkage studies are identified. These are:

  1. a)

    analysis of twin and family data have consistently failed to identify a single major gene effect upon schizophrenia risk;

  2. b)

    ascertainment of multiplex families does not guarantee the sampling of families who are segregating for the major gene, even if a major gene effect exists, and

  3. c)

    environmental influences appear to play an essential role in the etiology of at least some schizophrenia. The implications of these features for the design of linkage studies in schizophrenia are discussed.

This article is published simultaneously in Schizophrenia Bulletin (1989) 15:281–292

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Early TS, Reiman EM, Raichle ME, Spitznagel EL (1987) Left globus pallidus abnormality in never-medicated patients with schizophrenia. Proc Nat Acad Sci USA 84:561–563

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 Psychiatr Res 20:115–130

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Google Scholar 

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

    Article  Google Scholar 

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

    Article  PubMed  CAS  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 (in press)

    Google Scholar 

  • Gottesman II, McGue M (1989) Mixed and mixed-up models for the transmission of schizophrenia. In: Cichetti D, Grove W (eds) Thinking clearly about psychology: essays in honor of Paul E. Meehl. University of Minnesota Press, Minneapolis (in press)

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Gurling H (1986) Candidate genes and favoured loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer’s disease. Psychiatr Dev 4:289–309

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Holzman PS, Kringlen E, Matthysse S, Flanagan SD, Lipton RB, Cramer G, Levin S, Lange K, Levy DL (1988) A single dominant gene can account for eye tracking dysfunctions and schizophrenia in offspring of discordant twins. Arch Gen Psychiatr 45:641–647

    Article  PubMed  CAS  Google Scholar 

  • Iacono WG, Tuason VB, Johnson RA (1981) Dissociation of smooth pursuit and saccadic eye tracking in remitted schizophrenics. Arch Gen Psychiatr 38:991–996

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lander ES, Botstein D (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185–199

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • 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

    Article  PubMed  CAS  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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Meehl PE (1972a) A critical afterword. In: Gottesman II, Shields J (eds) Schizophrenia and genetics, a twin study vantage point. Academic, 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

    PubMed  CAS  Google Scholar 

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

    Article  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

    PubMed  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

    Article  Google Scholar 

  • Reveley AM, Reveley MA, Murray RM (1984) Cerebral ventricular enlargement in nongenetic schizophrenia: a controlled twin study. Br J Psychiatry 144:89–93

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 

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

    Google Scholar 

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

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Slater E, Cowie V (1971) The genetics of mental disorders, Oxford University 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

    Article  PubMed  CAS  Google Scholar 

  • St. George-Hyslop PH, Tanzi RE, Polinsky RJ et al. (1987) The genetic defect causing familial Alzheimer’s disease maps on chromosome 21. Science 235:885–890

    Article  Google Scholar 

  • Thoday JM (1967) New insights into continuous variation. In: Crow JF, Neel JV (eds) Proceedings of the 3rd international congress of human genetics. Johns Hopkins, University Press, Baltimore, pp 339–350

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    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

    Article  PubMed  CAS  Google Scholar 

  • Vogler GP, Gottesman II, McGue MK, Rao DC (1989) Mixed model segregation analysis in the Lindelius Swedish pedigrees. Behav Genet (in press)

    Google Scholar 

  • Wong DF, Wagner HN, Tune LE et al. (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558–1563

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

Download references

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

Editor information

Editors and Affiliations

  1. Hereditory Diseases Programme, World Health Organization, Avenue Appia, CH-1211, Geneva 27, Switzerland

    Victor Bulyzhenkov

  2. Fondation IPSEN pour la Recherche Therapeutique, 30, rue Cambronne, F-75737, Paris Cedex, France

    Yves Christen

  3. Division of Mental Health, World Health Organization, Avenue Appia, CH-1211, Geneva 27, Switzerland

    Leonid Prilipko (Senior Medical Officer) (Senior Medical Officer)

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

McGue, M., Gottesman, I.I. (1990). Genetic Linkage in Schizophrenia: Perspectives from Genetic Epidemiology. In: Bulyzhenkov, V., Christen, Y., Prilipko, L. (eds) Genetic Approaches in the Prevention of Mental Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-07421-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-07421-3_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-07423-7

  • Online ISBN: 978-3-662-07421-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation