The multi-ancestry meta-analysis method also allowed for tests of whether a variant effect size differed (that is, was moderated) by ancestry along four ancestry dimensions estimated from multidimensional scaling (MDS) of allele frequencies from each participating study (Fig. 1a). Roughly, the first axis represents an EAS ancestry cline, the second axis an AFR cline, the third a EUR cline (north to south EUR) and the fourth an AMR cline. There was minimal evidence of effect size moderation by ancestry for most independent variants, ranging from 76.6% (187 variants) in CigDay to 85.0% (175 variants) in SmkCes. Another 7.7–18.1% showed modest evidence for moderation. Finally, roughly 3.6% of all independent variants, reflecting 136 variants from 84 distinct loci, showed strong evidence of effect size moderated by ancestry (complete results are shown in Supplementary Table 2). Comparisons between the variants with strong evidence for effect size moderation by ancestry and those with no evidence suggested that the identification of these 136 variants was not driven to a large extent by differences in imputation quality, LD scores or Fst (fixation index) across ancestries.
