One such intermediate phenotype is an intense alcohol-related skin flushing reaction caused by several variants of alcohol-metabolizing enzymes, which were identified in the 1970s. This phenomenon, which has been observed for centuries in people of Japanese, Chinese, or Korean descent who consume alcohol, is associated with a decreased risk for AUD but is unrelated to other types of substance use disorder (SUD).11 The second intermediate phenotype, which enhances risk for both AUD and other types of SUD, is the long-known association between substance-related problems and impulsive-like or externalizing behaviors.12,13 The underlying characteristics include elevated levels of sensation seeking and behavioral/physiological disinhibition. These behaviors contribute to what has been referred to as type 2 and type B subtypes of AUD that are associated with an early onset of alcohol and other drug problems and a severe clinical course.14 A third intermediate group of phenotypes that also is related to increased risks for both AUD and other types of SUD operates through the presence of several additional major psychiatric conditions, such as schizophrenia and bipolar disorders.15,16 Finally, this abbreviated list of genetically
