Polygenic risk scores (PRS) were derived to test whether aggregate risk for SRE in the discovery set was associated with phenotype in the test set. We used weights from two discovery sets: i) the full meta-analysis; and ii) the ALSPAC-specific results, given evidence of heritability in ALSPAC but not S4S. The first test set involved participants (N=1,080; 61.1% male) with both genotype and phenotype data from the UCSF Family Alcoholism Study (Vieten et al., 2004). The sample was composed of small family pedigrees, which ranged in size from 3–20 individuals. The subsample used in the present study had an average age of 48.9 (SD=12.1) years. PLINK 1.9 (Chang et al., 2015) was used to derive PRS. We employed a linear mixed model with a kinship matrix fitted as a random effect to control for the relatedness among participants. Age, sex, and four ancestry PCs were included as covariates. The second dataset was from the Collaborative Study on the Genetics of Alcoholism (COGA). COGA is a multi-center study of families with alcohol dependence (AD). African American (AA) and European American (EA)
