One key factor in interpreting the differences between these traits and AD is that the distribution of consumption levels and AUDIT scores can be highly skewed in population samples, with most individuals at the low (non-pathological) end of the spectrum. This effect may be especially pronounced among the older, healthy volunteers of the UK Biobank cohort32 and in the 23andMe cohort, which is more educated and has higher socioeconomic status than the general US population18. We hypothesize that the variants that affect consumption at lower levels may differ substantively from those that affect very high levels of consumption in alcohol dependent individuals, who are also characterized by loss of control over intake33. This appears to be the case in studies that used specific cut-offs to harmonize AUDIT scores with AD data30,34. The larger of these studies30 reports that the genetic correlation between AD and AUDIT scores is maximized at an AUDIT cutoff ≥ 20 (with controls defined as those scoring ≤ 4; rg = 0.90). Interestingly, that study also found that a score reflecting items related to problem drinking (AUDIT-P)
