and the joint datasets (Supplementary Table 2). In the joint analysis, we observed highly significant associations between rs17664708 and CD (P=0.0023), AD (P=0.0076), ND (P=0.0026) and OD (P=0.00018). However, significant associations disappeared when subjects affected with CaD were excluded from AD (P=0.3), ND (P=0.069) and CD (P=0.053). Nonetheless, the association remained highly significant for OD when the CaD cases were excluded (P=0.0013), which suggests that rs17664708 could also be a risk variant for OD in AAs independent of CaD. Finally, to remove the confounding effect of OD, we tested the association between rs17664708 and CaD by either controlling for OD status in the regress model or excluding participants who are OD. The results remain significant in the joint datasets by OD status adjusted analysis (OR=2.03, 95% CI=1.17–3.55, P=0.011) or after excluding OD participants (OR=2.47, 95% CI=1.48–4.11, P=0.0003) arguing against the possibility that the significant associations between rs17664708 and CaD arise solely from OD. The association results from other SD might indicate that the association is not specific for CaD and could reflect a shared liability between different substances. The role of NRG1 in other SD remains to be further investigated.
