An interesting possible OD risk gene identified in Phase 1 was DISC1, which (among other functions) regulates development of the cerebral cortex. DISC1 was originally identified as a schizophrenia risk gene in a cytogenetic study (32) and considerable evidence since has tied it to cognitive phenotypes in human (33) and animal (34) models. We observed nominally significant associations with DISC1 in both EAs and AAs (meta p=5.2×10−6). Subsequent to this common-variant association finding, we used deep sequencing at this locus to identify a set of rare variants in DISC1 that contribute to risk for OD (35). Thus, this study ties OD to other cognitive phenotypes via a common gene, and, as schizophrenia was one of the five disorders identified as associated to calcium pathways (24), also through gene pathways. Previously, we reported that another schizophrenia-associated locus, NRG1, is associated with cannabis dependence in AAs (36).
