section_path: Causes/Genetic variation
section_name: Genetic variation
paragraph_text: Genetic variation
  
  There are genetic variations that affect the risk for alcoholism. Some of these variations are more common in individuals with ancestry from certain areas; for example, Africa, East Asia, the Middle East and Europe. The variants with strongest effect are in genes that encode the main enzymes of alcohol metabolism, ADH1B and ALDH2. These genetic factors influence the rate at which alcohol and its initial metabolic product, acetaldehyde, are metabolized. They are found at different frequencies in people from different parts of the world. The alcohol dehydrogenase allele ADH1B*2 causes a more rapid metabolism of alcohol to acetaldehyde, and reduces risk for alcoholism; it is most common in individuals from East Asia and the Middle East. The alcohol dehydrogenase allele ADH1B*3 also causes a more rapid metabolism of alcohol. The allele ADH1B*3 is only found in 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.