an extreme sampling design, are more powerful than community samples for investigations of genetic association with disorders like schizophrenia. However, when the goal is to test known schizophrenia genetic loci for association with known schizophrenia-relevant endophenotypes, a case–control study of schizophrenia necessarily confounds diagnostic status and endophenotype level, resulting in the possibility of spurious gene–endophenotype correlations (Iacono et al. 2016). That is, if the gene is associated with schizophrenia, and cases are known to have higher levels of the endophenotype than controls, then the gene will also be associated with the endophenotype regardless of its causal role in schizophrenia. The same will be true for any phenotype (e.g. education level, marital status, etc.) that is systematically different in individuals with schizophrenia.
