An empirical argument against pervasive rare variant effects is that common variants are often consistent across populations — such as between Caucasians and Asians — despite differences in allele frequencies65,66. If rare variants are recently derived relative to the common variants, then they should be at different frequencies in Caucasians and Asians, and we would expect that they would only induce synthetic common variant associations in one of these populations, or at least would not tend to have the same magnitude of effect. This would be especially true of common variants that differ in frequency between the two populations. Under a mutation-selection balance model, it may be possible for different novel rare variants to have effects in each population, and fine mapping studies sometimes reveal subtle differences in the patterns of association [eg.67,68. Nevertheless, the simplest interpretation of the consistency of common variant effects is that they are actually due to the common variants themselves or to unobserved common variants in high LD across all populations.
