Discovery GWAS were focused on the EA subsample and a trans-ancestral meta-analysis of GWAS summary statistics from the COGA AA and EA subsamples (EA+AA; see Figure 1). Even though a GWAS was conducted in the AA subsample, results were only used in the trans-ancestral meta-analysis. Due to the strict definition of AD controls, the individual AA subsample was too small for use as a discovery sample (both cases and controls had a sample size < 1000; full results available upon request). For binary traits, association analysis was performed using a generalized estimating equation (GEE) framework (with a binomial probability distribution) to control for relatedness with each family treated as a cluster. For the criterion count measure, a liner mixed effects model was fit to continuously distributed data with family relationship adjusted through a kinship matrix. The R package GWAF 40 was used to test both models. Birth cohort (birth year: 1890-1929; 1930-1949; 1950-1969; >=1970) was a stronger predictor of alcohol dependence than was age (see also: Grucza et al., 2008 41), and hence was selected along with sex, GWAS array