PENETRANCE OF SCHIZOPHRENIA-RELATED DISORDERS IN MULTIPLEX FAMILIES AFTER CORRECTION FOR ASCERTAINMENT

Penetrance of schizophrenia and related disorders was calculated in 27 multiplex pedigrees ascertained by a consistent set of screening and selection criteria. The rationale for the study was that single major locus linkage models are frequently used on a pragmatic basis to analy ze data for schizophrenia which is most likely to have a polygenic mec hanism. Penetrance estimates assuming Mendelian inheritance represent maximum values and thus can provide guidance for construction of appro priate linkage models. Four diagnostic models were considered: narrow (schizophrenia and chronic schizoaffective disorder), intermediate (in cluding other non-affective psychoses), broad (including schizotypal a nd paranoid personality disorders), and broad + suspected (including s uspected schizophrenia spectrum disorders). Penetrance was calculated in the youngest affected adult sibship, under both dominant and recess ive inheritance assumptions, either without correction, or with a corr ection that excluded individuals necessary to meet pedigree selection criteria. Without correction, penetrance values ranged from 0.70 to 0. 90 assuming dominant and 1.0 to >1.0 assuming recessive inheritance. A fter correction, the ranges were 0.30-0.51 for dominant and 0.47-0.59 for recessive models. The corrected values are likely to be overestima tes given that the penetrance of any one locus in a multilocus model m ust be lower. It is suggested that lod score analyses of schizophrenia should attempt to derive information primarily from affected diagnose s, because information derived from unaffecteds under high penetrance models is likely to be spurious. (C) 1996 Wiley-Liss, Inc.