that there is a measurable effect in vivo30. Although some individuals with the ADH1B*48His allele report flushing upon consuming alcohol, it does not approach the dramatic Asian flushing reaction caused by the ALDH2*504K allele, nor does it lead to the large increase in circulating acetaldehyde characteristic of ALDH2*504K carriers. Nevertheless, the ADH1B*48His allele is nearly as protective as the heterozygous state of ALDH2*504K, with odds ratios for heterozygous carriers between 0.2 and 0.420, 21, 31-33. It is thought that the faster metabolism of ethanol produces at least a transient increase in acetaldehyde in the liver which in turn triggers an aversive reaction. The protective ADH1B*48His allele is found at high frequency in East Asia, with over 90% of Chinese and Japanese carrying at least one copy of the allele; it is at low frequency in Europe and Africa (generally under 5%), and at modest frequency (about 20%) in populations from the Middle East34-37. Because of its low allele frequency in Europeans, and its absence from arrays used in genome-wide association studies (GWAS), effects in people of European descent have, until recently, been hard to establish. A recent study demonstrated that ADH1B*48His has a similar effect on risk for alcoholism in
