Additionally, these studies relied almost exclusively on a candidate gene approach. Examples of the genes studied are SLC6A4 (i.e., the short, long 5-HTTLPR variant); DRD4; GABRA2; ADH1B; and ALDH2. Unfortunately, the replication of findings from candidate GxE studies can be challenging; most often noted are inconsistencies reported for the relationship between the 5-HTTLPR variant and stressful life events (see Duncan and Keller6 and Dick et al.5 for an expanded discussion of this topic). Some studies did examine candidate genes with relatively well-understood biological mechanisms related to alcohol consumption and AUD (e.g., ADH1B and ALDH2; see Hurley et al.53), and a few tested multiple markers or a sum score of risk variants across multiple genes28,45. However, other techniques, including polygenic risk scores that aggregate the effect of a number of gene markers, offer researchers newer alternatives that could help to increase confidence in the genetic associations that are being studied54,55. Studies using a polygenic score approach were not represented in the literature we reviewed.
