Biologically relevant combinations of functional variants within gene networks are likely to have additive effects on risk for addiction. However, even with high frequency variants very large sample sizes are required to detect differences between carriers of different genotype combinations. Recent exploratory studies in European-ancestry and African American samples, but not yet in AI/AN samples, indicate that these kinds of studies might result in pharmacogenetic therapeutics, i.e. the determination of individualized responses to medications for the treatment of AUD (reviewed in Enoch41).
