LD scores are associated with differences in allele frequencies between populations but LD score regression can still distinguish confounding from polygenicity.

The linkage disequilibrium (LD) score regression method tests whether there is an association between the LD score and allele frequency differences between cases and controls. It makes the assumption that there is no association between LD score and allele frequency differences among populations and hence that any observed association is the result of a polygenic effect rather than population stratification. This assumption was previously tested only using European cohorts. In comparisons among more diverse HapMap populations, we observe that there is indeed an association between the LD score and allele frequency differences. However, this effect is small and when we carry out simulations of large case-control samples, the effect becomes negligible. We conclude that if the intercept is small then any increase in mean chi-squared does indeed reflect a polygenic effect rather than population stratification.