In the present study, using new analytic strategy and integrating evidence from the functional analysis, we identified a risk region for alcohol dependence (i.e., PHF3-PTP4A1 locus) that was missed previously. This region was enriched with functional genetic SNPs that had replicable associations with alcohol dependence. This important risk region was not reported previously, because most of the risk SNPs in it had p-values between 10−5 and 10−3 that were out of the top-ranked risk SNP list (p<10−5) in previous GWASs. Such p values were reasonable for alcohol dependence, because the effect sizes of individual loci for this complex trait had to be small. We used a replication design to reduce the false positive rate and increase the significance threshold (α) from 5×10−8, and thus discovered this risk region.
