Early studies compared SR in individuals (mostly males) with (FH+) and without (FH-) a history of alcohol dependence in order to demonstrate that individual differences in SR could be considered genetically-linked determinants of alcohol use disorder. Non-placebo controlled studies conducted by Schuckit and colleagues found that FH+ males experienced less of the aversive effects of alcohol as compared to FH- males matched on key demographic and body mass variables.[1] Furthermore, FH+ young males and their fathers showed similar SR after reaching peak BAC, suggesting that SR is a heritable risk factor for the development of alcohol use disorder.[3] Schuckit's placebo-controlled studies generally reported lower SR among FH+, as compared to FH-, subjects along declining BAC, with differences more evident among men than women. Additional studies found that FH+ subjects who experienced low-level of response were more than 4 times as likely to meet criteria for alcohol use disorder at 10-year follow-up as compared to FH- subjects who reported the same SR pattern.[5] Subsequent follow-up studies conducted primarily by Schuckit's group established that low-level of response is a genetically-linked risk factor for alcohol use disorder, which is not better explained by robust confounding factors such as age of first drink, current alcohol use and impulsivity.[3][6] A 1992 meta-analysis further buttressed the Low Level of Response Model by reporting that sons of alcoholics exhibited lower responses to alcohol on both the ascending and descending limbs of the BAC curve.