The genome-wide significant locus on chromosome 8 was replicated in an independent Icelandic sample consisting of 5,501 cases with CUD and 301,041 population controls (deCODE cohort). The cases were diagnosed with CUD while undergoing inpatient treatment at the SSA National Center of Addiction Medicine, Vogur Hospital in Iceland (www.saa.is). SAA treats around ~80% of individuals with substance abuse in Iceland which makes the deCODE CUD cohort nearly population-wide20. We tested nine variants located in the risk locus in the Icelandic sample; the index variant and eight correlated variants (0.2< r2 <0.7) with P-values less than 1x10−6 (four genome-wide significant). All variants demonstrated consistent direction of association. The most strongly associated variant (rs56372821) in the discovery GWAS showed a P-value of 3.27x10−3 in the deCODE cohort , however with a slightly smaller effect size (Table 1). In the meta-analysis, rs56372821 showed a little stronger association with CUD (P=9.09x10−12), and additional two variants became genome-wide significant (Table 1).
