Across phenotypes, 88 of these 136 variants showed moderation by the first axis of ancestry variation (approximate EAS cline; Fig. 1b, left), 29 variants by the second axis (approximate AFR cline; Fig. 1b, middle) and 10 variants by the fourth axis (approximate AMR cline; Fig. 1b, right). Nine variants showed differences in effect size moderated by the third axis (EUR cline). Only the effect of one variant was moderated by three or more ancestry clines (EAS, AFR and AMR): rs1229984, a missense variant in the alcohol dehydrogenase gene ADH1B, which has been shown to be protective against alcohol consumption9. An increase on any of these clines was associated with a reduced effect size of this allele, on average. For example, if there are two people who both carry one copy of the protective T allele for this variant but are separated by 1 s.d. on MDS component 1 (EAS cline), the person with a lower value on that MDS cline would be expected to drink 0.3 fewer drinks than the person with a higher MDS value, despite the same rs1229984 genotype in ADH1B.
