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Familial–sporadic schizophreniaSubtyping schizophrenia by the presence/absence of a positive family history for schizophrenia spectrum disorders was proposed in the 1980s as a strategy expected to be more successful in resolving heterogeneity than symptom-based typologies.152 Although inclusion/exclusion criteria varied across studies, 'familial' (F) cases were typically defined as having By and large, the F/S classification has not been successful in identifying homogeneous phenotype groups for genetic research. The dichotomy, based on recurrence of manifest schizophrenia among biological relatives, might easily result in a misclassification unless: (i) ascertainment of all family members is complete; (ii) appropriate adjustments for family size, age, and lifetimes at risk are made; and (iii) the spectrum of disorders counted as recurrence cases is stringently defined. However, even if such confounding factors are adequately controlled for, and 'familiality' is represented as a continuous trait rather than a dichotomy,173 the method remains open to error due to the likely presence of unexpressed genotypes in schizophrenia families.39 Moreover, simulation power analyses174 suggest that the F/S design can be useful only in the context of very large samples of nuclear families. Date: 2016-04-22; view: 861
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