NrCAM 5’ flanking region haplotypes, however, displayed association with the same phase in each of these three samples (p = 0.0002, p = 0.06 and p = 0.02, respectively). Further, an additional independent sample that compared haplotype frequencies in 288 alcohol-dependent Japanese subjects vs 472 matched controls also displayed highly-significant association (p < 0.01) with the same phase. These cumulative observations strongly supported the idea that NrCAM variants provide polygenic contributions to human interindividual differences in addiction vulnerability. They contrast with the failure to identify such reproducibly-positive findings at the adjacent genes including LAMB1, LAMB4 and iPLA2.
