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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1983 Nov;35(6):1161–1178.

The transmission of schizophrenia under a multifactorial threshold model.

M McGue, I I Gottesman, D C Rao
PMCID: PMC1685995  PMID: 6650500

Abstract

Family studies of schizophrenia have reported elevated rates of both definite and definite-plus-probable schizophrenia among the relatives of definite schizophrenics. These elevated rates imply a strong association between the two forms of diagnosis and suggest some form of familial transmission. Here we have used recently developed maximum likelihood methods to investigate this association and characterize the nature of the familial transmission. Results indicated that although the two forms of diagnosis were strongly related, they could not be considered alternative manifestations of a single liability distribution. Heritability estimates for either form of diagnosis were comparable (h2 = .668 +/- .052 and c2 = .191 +/- .038 for definite while h2 = .628 +/- .073 and c2 = .236 +/- .106 for definite-plus-probable), although cultural transmission (i.e., c2) was statistically significant only for definite-plus-probable. For either form of diagnosis, residual twin resemblance was statistically significant and could not be explained in terms of the effects of genetic dominance. These results are comparable to those of an earlier analysis based upon a similar data set. Finally, the statistical correction used to adjust for between-study heterogeneity in morbidity risk figures did not noticeably alter the parameter estimates.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carter C. L., Chung C. S. Segregation analysis of schizophrenia under a mixed genetic model. Hum Hered. 1980;30(6):350–356. doi: 10.1159/000153156. [DOI] [PubMed] [Google Scholar]
  2. Debray Q., Caillard V., Stewart J. Schizophrenia: a study of genetic models. Hum Hered. 1979;29(1):27–36. doi: 10.1159/000153012. [DOI] [PubMed] [Google Scholar]
  3. ESSEN-MOLLER E. The calculation of morbid risk in parents of index cases, as applied to a family sample of schizophrenics. Acta Genet Stat Med. 1955;5(4):334–342. doi: 10.1159/000150781. [DOI] [PubMed] [Google Scholar]
  4. Elston R. C. Discussion: Methodologies in human behavior genetics. Soc Biol. 1973 Sep;20(3):276–279. doi: 10.1080/19485565.1973.9988054. [DOI] [PubMed] [Google Scholar]
  5. Endicott J., Nee J., Fleiss J., Cohen J., Williams J. B., Simon R. Diagnostic criteria for schizophrenia: reliabilities and agreement between systems. Arch Gen Psychiatry. 1982 Aug;39(8):884–889. doi: 10.1001/archpsyc.1982.04290080006002. [DOI] [PubMed] [Google Scholar]
  6. Gottesman I. I., Shields J. A polygenic theory of schizophrenia. Proc Natl Acad Sci U S A. 1967 Jul;58(1):199–205. doi: 10.1073/pnas.58.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Karlsson J. L. Family transmission of schizophrenia: a review and synthesis. Br J Psychiatry. 1982 Jun;140:600–606. doi: 10.1192/bjp.140.6.600. [DOI] [PubMed] [Google Scholar]
  8. Kety S. S., Rosenthal D., Wender P. H., Schulsinger F. Studies based on a total sample of adopted individuals and their relatives: why they were necessary, what they demonstrated and failed to demonstrate. Schizophr Bull. 1976;2(3):413–428. doi: 10.1093/schbul/2.3.413. [DOI] [PubMed] [Google Scholar]
  9. Kidd K. K., Cavalli-Sforza L. L. An analysis of the genetics of schizophrenia. Soc Biol. 1973 Sep;20(3):254–265. doi: 10.1080/19485565.1973.9988051. [DOI] [PubMed] [Google Scholar]
  10. Matthysse S. W., Kidd K. K. Estimating the genetic contribution to schizophrenia. Am J Psychiatry. 1976 Feb;133(2):185–191. doi: 10.1176/ajp.133.2.185. [DOI] [PubMed] [Google Scholar]
  11. Morton N. E., MacLean C. J. Analysis of family resemblance. 3. Complex segregation of quantitative traits. Am J Hum Genet. 1974 Jul;26(4):489–503. [PMC free article] [PubMed] [Google Scholar]
  12. O'Rourke D. H., Gottesman I. I., Suarez B. K., Rice J., Reich T. Refutation of the general single-locus model for the etiology of schizophrenia. Am J Hum Genet. 1982 Jul;34(4):630–649. [PMC free article] [PubMed] [Google Scholar]
  13. Paykel E. S. Contribution of life events to causation of psychiatric illness. Psychol Med. 1978 May;8(2):245–253. doi: 10.1017/s003329170001429x. [DOI] [PubMed] [Google Scholar]
  14. Rabkin J. G. Stressful life events and schizophrenia: a review of the research literature. Psychol Bull. 1980 Mar;87(2):408–425. [PubMed] [Google Scholar]
  15. Rao D. C., Morton N. E., Cloninger C. R. Path analysis under generalized assortative mating. I. Theory. Genet Res. 1979 Apr;33(2):175–188. doi: 10.1017/s0016672300018310. [DOI] [PubMed] [Google Scholar]
  16. Rao D. C., Morton N. E., Gottesman I. I., Lew R. Path analysis of qualitative data on pairs of relatives: application to schizophrenia. Hum Hered. 1981;31(6):325–333. doi: 10.1159/000153233. [DOI] [PubMed] [Google Scholar]
  17. Rao D. C., Morton N. E., Lalouel J. M., Lew R. Path analysis under generalized assortative mating. II. American I.Q. Genet Res. 1982 Apr;39(2):187–198. doi: 10.1017/s0016672300020875. [DOI] [PubMed] [Google Scholar]
  18. Reich T., James J. W., Morris C. A. The use of multiple thresholds in determining the mode of transmission of semi-continuous traits. Ann Hum Genet. 1972 Nov;36(2):163–184. doi: 10.1111/j.1469-1809.1972.tb00767.x. [DOI] [PubMed] [Google Scholar]
  19. Rice J. P., Nichols P. L., Gottesman I. I. Assessment of sex differences for multifactorial traits using path analysis: application to learning difficulties. Psychiatry Res. 1981 Jun;4(3):301–312. doi: 10.1016/0165-1781(81)90032-9. [DOI] [PubMed] [Google Scholar]
  20. SCHOFIELD W., BALIAN L. A comparative study of the personal histories of schizophrenic and nonpsychiatric patients. J Abnorm Soc Psychol. 1959 Sep;59:216–225. doi: 10.1037/h0042510. [DOI] [PubMed] [Google Scholar]
  21. Shields J., Gottesman I. I. Cross-national diagnosis of schizophrenia in twins. The heritability and specificity of schizophrenia. Arch Gen Psychiatry. 1972 Dec;27(6):725–730. doi: 10.1001/archpsyc.1972.01750300005001. [DOI] [PubMed] [Google Scholar]
  22. Smith C. Statistical resolution of genetic heterogeneity in familial disease. Ann Hum Genet. 1976 Jan;39(3):281–291. doi: 10.1111/j.1469-1809.1976.tb00132.x. [DOI] [PubMed] [Google Scholar]
  23. Tsuang M. T., Bucher K. D., Fleming J. A. Testing the monogenic theory of schizophrenia: An application of segregation analysis to blind family study data. Br J Psychiatry. 1982 Jun;140:595–599. doi: 10.1192/bjp.140.6.595. [DOI] [PubMed] [Google Scholar]
  24. Vaughn C. E., Leff J. P. The influence of family and social factors on the course of psychiatric illness. A comparison of schizophrenic and depressed neurotic patients. Br J Psychiatry. 1976 Aug;129:125–137. doi: 10.1192/bjp.129.2.125. [DOI] [PubMed] [Google Scholar]

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