50% of variation in liability to SNPs with MAF < 0.1, SNPs with MAF > 0.4 explained only 5% (s.e. 0.3%) of the variance, which is only 10% of the variation explained by all SNPs (Figure 1c,d; Supplementary Tables 5–6). Furthermore, our simulation strategy is a best case scenario in favour of the rare variants only model since our simulation extends the frequency of “rare” variants to MAF of 0.1 generating higher LD between the common genotyped SNPs and causal variants than would be expected under a more usual MAF definition of “rare”. Our results are consistent with analyses of the ISC data8,20. In the Supplementary Note we contrast our methods to the risk profiling methods used by the ISC and the efficient mixed model association expedited (EMMAX) method of Kang et al21.
