A subtler example arises from the association of ALDH2 with alcohol consumption. This gene encodes aldehyde dehydrogenase, an enzyme responsible for metabolizing acetaldehyde (a metabolite of alcohol) to acetic acid. When less of this enzyme is present, acetaldehyde can build up after alcohol consumption, leading to unpleasant side effects. Therefore, the minor allele is robustly associated with reduced alcohol consumption [19]. The frequency of the minor allele at the ALDH2 locus is very low in samples of European ancestry but is relatively common in samples of East Asian ancestry. It is, therefore, only associated with alcohol consumption in the latter population. As a result, in GWAS of high blood pressure, ALDH2 was not identified in studies that recruited predominantly European samples [20] but was identified in studies that recruited East Asian samples (once genotyping chips that adequately tagged the ALDH2 locus were used) [21,22]. This confirms the results of Mendelian randomization analyses of alcohol consumption and blood pressure conducted prior to these later GWAS [23]. In other words, alcohol consumption causes high blood pressure, and this is detected in GWAS
