What this means

ADH1B codes for alcohol dehydrogenase 1B, the enzyme that converts ethanol to acetaldehyde. The R48H "fast" allele (rs1229984) makes the enzyme dramatically more active — up to 40x faster in vitro. The result is that ethanol is converted to acetaldehyde more quickly, which (if ALDH2 can't keep up) leads to flushing and a less pleasant drinking experience. The fast allele is concentrated in East Asian populations and pockets of the Middle East, and is strongly protective against alcohol use disorder.

When you drink alcohol, the first step in breaking it down is an enzyme called ADH1B. One common version of this gene makes a "fast" enzyme — up to forty times more active. That converts alcohol into a toxic in-between substance (acetaldehyde) very quickly. If your next enzyme can't clear acetaldehyde fast enough, you flush, feel queasy, and don't really enjoy drinking. The fast version is concentrated in East Asian populations and parts of the Middle East, and it strongly protects against developing problems with alcohol.

Caveats

• Often paired with the ALDH2 flush variant; together they magnify each other's effects.
• Fast metabolism does not mean alcohol is processed without harm — the toxic intermediate is just produced faster.
• The protective effect against alcohol use disorder is one of the cleanest examples in psychiatric genetics.
• Allele frequency varies enormously by ancestry.

References

• Edenberg — The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants (Alcohol Research & Health, 2007)
• Bierut et al. — ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry (Molecular Psychiatry, 2012)