Genetic analysis of schizophrenia as an example of a putative multifactorial trait

A new method for analysis of multifactorial traits is described which involves mathematical definition of MZ and DZ twin concordances in terms of penetrance and the number of contributory genes. This allows the number of major genes and their joint penetrance to be estimated. Application to familial schizophrenia indicates causation by a single dominant allele, a deduction supported by several treatments of observed risks in other family members. Lifetime empiric risks are analysed in the context of four conditions: genetic predisposition, prenatal trauma, psychological or other trauma in early adult life and possible exacerbation of symptoms associated with close contact with affected family members. Comparative empiric risks for twins and sibs are explained by consideration of coincident gestations, season of birth and the sharing of a chorionic sac and foetal blood supply. The data are consistent with penetrance being complete in homozygotes and generally around 0.33 in heterozygotes, but it increases in additive fashion depending on risk factors associated with the type of relationship with one or more affected family members and factors associated with twinning. The influence of an affected parent is nearly 3 times as great as that of an affected sibling. The population frequency of heterozygotes is deduced to be around 2.6%.