Thus, this locus has produced genome-wide significant evidence for association to BIP,66 with evidence for broader set of associated phenotypes (especially SCZ).36,75 The inconsistency of results in large MDD and BIP replication samples suggests that the current finding should be viewed with caution. If specific genetic variants can be identified that underlie the BIP association in this region, it will be possible to evaluate their degree of association with other phenotypes including MDD. A continuing challenge in this field is the differentiation between true pleiotropy (genetic risk factors associated with distinct phenotypes) versus diagnostic misclassification (phenotypic overlap in cases with different genetic risk factors, leading to diagnostic ‘error’). There is a robust and evolving literature in psychiatric genetic epidemiology regarding the degree of independence versus co-segregation of current diagnostic categories, as well as the occurrence and familial risks of cases with mixed syndromes and changes in clinical syndromes over time. It is likely that analyses of large-scale genomic data will provide new perspectives on these issues.
