some individuals of African descent and certain Native American tribes. African Americans and Native Americans with this allele have a reduced risk of developing alcoholism. Native Americans, however, have a significantly higher rate of alcoholism than average; risk factors such as cultural environmental effects (e.g. trauma) have been proposed to explain the higher rates. The aldehyde dehydrogenase allele ALDH2*2 greatly reduces the rate at which acetaldehyde, the initial product of alcohol metabolism, is removed by conversion to acetate; it greatly reduces the risk for alcoholism. A genome-wide association study (GWAS) of more than 100,000 human individuals identified variants of the gene KLB, which encodes the transmembrane protein β-Klotho, as highly associated with alcohol consumption. The protein β-Klotho is an essential element in cell surface receptors for hormones involved in modulation of appetites for simple sugars and alcohol. Several large GWAS have found differences in the genetics of alcohol consumption and alcohol dependence, although the two are to some degree related. DNA damage Alcohol-induced DNA damage, when not properly repaired, may have a key role in the neurotoxicity induced by alcohol. Metabolic conversion of ethanol to acetaldehyde can occur in the brain and the neurotoxic effects of ethanol appear to be associated with acetaldehyde induced DNA damages including DNA adducts and crosslinks. In addition to acetaldehyde, alcohol metabolism produces potentially genotoxic reactive oxygen species, which have been demonstrated to cause oxidative DNA damage. Diagnosis Definition Misuse, problem use, abuse, and heavy use of alcohol refer to improper use of alcohol, which may cause physical, social, or moral harm to the drinker. The Dietary Guidelines for Americans, issued by the United States Department of Agriculture (USDA) in 2005, defines "moderate use" as no more than two alcoholic beverages a day for men and no more than one alcoholic beverage a day for women. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as the amount of alcohol leading to a blood alcohol content (BAC) of 0.08, which, for most adults, would be reached by consuming five drinks for men or four for women over a two-hour period. According to the NIAAA, men may be at risk for alcohol-related problems if their alcohol consumption exceeds 14 standard drinks per week or 4 drinks per day, and women may be at risk if they have more than 7 standard drinks per week or 3 drinks per day. It defines a standard