Abstract
Simulated pedigrees of schizophrenia generally show a clear peak in their likelihood surface corresponding to analysis by the genetic models, which served as the basis for the simulation. The likelihood surface obtained with real data permits determination of the allelic frequency and the selection of an optimal one-locus, two-locus, and four-locus model. These three models have certain features in common, notably, a relatively high frequency of the allele predisposing to schizophrenia (about 20%) and a relatively low index of genetic determination (23%--34%). However, direct likelihood comparisons do not permit distinctions between the one-locus, two-locus, and four-locus models. The most likely interpretation of this finding is that the etiology of schizophrenia is heterogeneous or even nongenetic. However, a simple model with a single completely recessive locus and incomplete penetrance in the homozygote also produces a flat likelihood surface closely resembling that obtained with the real data. With reservation, this single-locus model may be put forward as a potentially useful working hypothesis.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Debray Q., Caillard V., Stewart J. Schizophrenia: a study of genetic models and some of their implications. Neuropsychobiology. 1978;4(5):257–269. doi: 10.1159/000117639. [DOI] [PubMed] [Google Scholar]
- Elston R. C., Campbell M. A. Schizophrenia: evidence for the major gene hypothesis. Behav Genet. 1970 Feb;1(1):3–10. doi: 10.1007/BF01067366. [DOI] [PubMed] [Google Scholar]
- Elston R. C., Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. doi: 10.1159/000152448. [DOI] [PubMed] [Google Scholar]
- Kessler S. Progress in research on the genetics of schizophrenia. Schizophr Bull. 1976;2(3):434–439. doi: 10.1093/schbul/2.3.434. [DOI] [PubMed] [Google Scholar]
- 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]
- Kringlen E. Twins--still our best method. Schizophr Bull. 1976;2(3):429–433. doi: 10.1093/schbul/2.3.429. [DOI] [PubMed] [Google Scholar]
- Stewart J. Schizophrenia: the systematic construction of genetic models. Am J Hum Genet. 1980 Jan;32(1):47–54. [PMC free article] [PubMed] [Google Scholar]