A two-gene model for schizophrenia with the possibility to detect carriers of the modifier gene

Abstract

A two-gene model for the hereditary transmission of schizophrenia is presented involving two pairs of autosomal alleles Ss and Pp. It is hypothesized that the recessive gene can produce schizophrenia in homozygous state with a penetrance of .40. In the presence of the gene P schizophrenia can occur in the heterozygote Ss, resulting in a more serious form of the disease and having a manifestation rate of .70. The population frequencies best fitting the available data are estimated to be approximately .03 for P and .07 or .08 for s. It is also hypothesized that the reproductive fitness is .80 in manifest schizophrenics with genotype ss pp and .50 in overt schizophrenics carrying the modifier gene P. The model is proposed to cover only the so-called "process" or "nuclear" type of schizophrenia. The remaining schizophrenics of "reactive" and other types may belong to different genotypes or consist in phenocopies. The model is discussed in relation to literature observations and our own previous studies. The possibilities for increased fitness of non-schizophrenic carriers of P and s are also discussed.