A potential confounding factor in comparing the population-based and clinically ascertained samples is the difference in age between sample types. The ALSPAC and FT12 samples are young adults, aged approximately 17 to 26, while the COGA and IASPSAD samples, being initially recruited from treatment-seeking patients, include many more middle-aged and older adults. There are known differences in the heritability of alcohol use between adolescence and adulthood (Edwards and Kendler, 2013; Bergen et al., 2007), which may affect cross-sample replication. To reduce this possibility, we also conducted the same GWAS procedure in a subset of the COGA families of corresponding age to ALSPAC/FT12 (age < 27, n = 879) who were mostly ascertained as children or extended family members of the recruited probands. We use these to supplement polygenic risk score analyses in the larger sample. There were too few individuals of comparable age in IASPSAD to perform complementary analyses.
