We also identified a novel GWS association (P = 5.57 × 10−10) with rs1437396, which is located between and within 10 kb of MTIF2 (mitochondrial translational initiation factor 2) and CCDC88A (coiled-coil domain containing 88A) on chromosome 2, a risk locus that was supported by evidence in both the EA and AA samples. This region is distinct from the chromosome 2 association previously identified in the German replication sample.9 CCDC88A appears to be the more promising candidate functionally. It interacts with DISC1,29,30 a gene originally known as a schizophrenia risk locus, but has been shown by us to be associated with opioid dependence.2,31 The protein product of this gene also interacts with VEGFA,32 a locus important for antidepressant response33 and hippocampal morphology.34 Further, the region was implicated in a previous linkage study,35 in which follow-up with SNPs mapping under the linkage peak also resulted in an association (empirical P < 0.02) with MTIF2. We found that CCDC88A, but not MTIF2, is differentially expressed in AD, supporting the possible importance of the former locus in AD.
