ALDH2 and ADH1B show the largest effect on risk for alcoholism of any known genes. There are smaller effects of variants in other alcohol dehydrogenases, particularly ADH1C and ADH4†, and reports of modest effects of other aldehyde dehydrogenase genes20, 33, 38-40. However, studies have been complicated by the fact that many variants among the ADH genes are in significant linkage disequilibrium (co-inherited). Another complication is that some of the functional variants with strongest effects on drinking (ADH1B*48His, ADH1B*370Cys and ALDH2*504K) are uncommon or rare in European populations, making many studies underpowered. Despite the strong effects of variations in these metabolism-related genes, they do not account for all of the genetic contribution to risk for alcoholism, particularly in populations (such as those from Europe) in which the allele frequencies for the variants with strongest effects are very low.
