Heritability enrichment of these statistics was tested by the LD Score partitioned heritability procedure. We derived binary annotations from the natural selection metrics by dichotomizing at extreme cutoffs defined by the top 2%, 1% and 0.5% of the values of each metric in the full set of SNPs. This approach is widely used in evolutionary genomics, owing to the difficulty of setting specific thresholds to define regions under selection28,51. Consistent with the previously described LDSR partitioned heritability protocol, enrichment was estimated with all binary annotations included in a model with multiple categories that represent important genomic features. This model included the 3 main categories of our set-based analysis (‘non-genic’, ‘genic’ and ‘LoF intolerant’), 2 categories based on genomic regions with outlying LD patterns (recombination hotspots and coldspots)98 and the 53 ‘baseline’ categories of Finucane et al.26.
