Phenotypic variation between parent–offspring trios and non-trios in genetic studies of schizophrenia

BackgroundPhenotypic differences between parent–offspring trios and non-trios have been reported for various psychiatric disorders, and it has been suggested that this may make comparisons of case-control and family-based results for gene-disease association studies inappropriate.AimsTo compare phenotypes between trios and non-trios with schizophrenia, and explore possible reasons for differences observed.MethodPhenotypes were compared between trios (n = 75) and non-trios (n = 424) collected as part of a case-control study.ResultsDifferences were observed for most phenotypes investigated, although all were eliminated after adjusting for confounding.ConclusionsConfounding, genetic heterogeneity or selection bias could result in differences in case-control and family-based results. However as we discuss, where adequately designed case-control studies are used, gene-disease association results would be incomparable between family-based and case-control studies only if genetic heterogeneity was present. These results do not support the presence of such genetic heterogeneity in schizophrenia.