Heritability of schizophrenia and major affective disorder as a function of age, in the presence of strong cohort effects.

It remains unclear whether age at onset for major psychiatric disorders is a useful marker of etiologic and genetic heterogeneity. The authors examined how heritability of schizophrenia and major affective disorders varied with age at onset. The sample was drawn from a large archival data set collected by Lionel Penrose, comprising 3,109 families with two or more members first hospitalized in Ontario between 1874 and 1944. The authors studied 1,295 sibships with schizophrenia (n = 487), major affective disorder (n = 378), both (n = 234) or neither (n = 196) of these disorders. Proportional hazards models were used to estimate how the hazard of hospitalization for each disorder (schizophrenia or major affective disorder) varied with proband age at onset, adjusted for changes in age at onset distribution between 1874 and 1944. A sibling's risk of hospitalization for the same illness significantly increased for each 10-year decrease in age at onset of the proband both for schizophrenia (hazard ratio = 1.21, 95 % confidence interval: 1.06, 1.39), and for affective disorder (hazard ratio = 1.29,95 % CI: 1.14, 1.45). Gender of proband was unrelated to sibling risk of the same illness, and tests of interaction effects between proband age at onset and gender on sibling risk were nonsignificant.