The variants located within or near SERINC2, KIAA0040, MREG-PECR or PKNOX2 were significantly associated with alcohol dependence at the genome-wide level (p < 5 × 10(-8) ) in meta-analysis or combined samples, and these associations were replicable across at least one sample.
We identified a unique genome-wide significant gene--KIAA0040--that was enriched with many replicable risk SNPs for AD, all of which had significant cis-acting regulatory effects.
The top hit of PKNOX2 (rs750338 with p=1.47 × 10(-6)) in the meta-analysis was replicated with the Australian Twin-Family Study of 778 families (p=1.39 × 10(-2)) Furthermore, several flanking SNPs of the top hits in the meta-analysis demonstrated borderline associations with alcohol dependence in the family sample (top SNPs were rs2269655, rs856613, and rs10496768 with p=4.58 × 10(-3), 2.1 × 10(-4), and 2.86 × 10(-3) for KIAA0040, NRD1 and THSD7B, respectively).