Alcohol dependence as defined by DSM-IV is complex, and association studies with more biologically refined (endo) phenotypes will help to disentangle this heterogeneity. Our approach of selecting more genetically homogeneous groups by stratifying for male sex and and an earlier age at onset is a first step in this direction. We must point out, however, that in order to achieve our overall sample of more than 1500 patients, it was necessary to relax our early age at onset criteria. While in the GWAS patients the upper inclusion limit was 28 years with a median of 20 years, the upper inclusion limit in the replication sample had to be extended to 45 years with a median of 30 years. Although, this cannot be considered as a specifically early age at onset, the sample as a whole and especially the GWAS sample has clearly been stratified for early age at onset.
