Until recently the only genes established to affect risk for AD were those encoding several alcohol metabolizing enzymes, but several other genes can now be regarded as confirmed risk loci (GABRA2; (refs. 12–15)), or strong candidates based on published data (e.g., CHRM2; (16, 17)). Further, the data supporting a relationship of ADH and ALDH loci to AD risk are now much richer, and effects at these loci are recognized in many more populations than previously (17–22). Although the mechanism of action of the effects of alcohol-metabolizing enzymes on AD risk is thought to be well understood, we are still in the early stages of understanding the core physiology of other risk loci. It is clear that only a small number of the many genes that influence risk for AD have been identified; and that the effects of many of the identified loci vary by population.
