The standardized effect size (z′) analysis for Fig. 2a was performed as follows. To avoid double-counting of SNPs/loci, we constrained analysis for each trait to (1) the single previous report that (2) did not combine genome-wide genotypes with focused platforms such as the metabochip, (3) reported the direction of effect with the allele in the GWAS Catalog and (3) included the maximum total number of individuals after applying criteria (1) and (2). (1) We selected a single manuscript, because many traits already have serial meta-analyses published, where earlier publications represent a subset of individuals reported in later publications, so reported effect sizes in the GWAS Catalog are not necessarily independent. (2) We excluded meta-analyses using mixtures of agnostic GWAS data (consistent map density across the genome) with focused platforms (for example, metabochip, oncochip or exomechip), because the actual sample size varies markedly across the genome, with overlapping agnostic/focused regions having substantially greater numbers of individuals in the analysis. Most of these reports fail to specify the sample size on a per-SNP basis, making it impossible to confidently calculate z′. (3)
