(Extended Data Fig. 11b, c) was calculated by first linkage disequilibrium pruning the results without regard to significance (pruning parameters in PLINK:– –indep-pairwise 1000kb 25 0.1). The t-statistics of the regression coefficients from the pruned results are then corrected for the effects of ‘winner’s curse’ and the variance explained by each SNP after accounting for covariate effects is summed across SNPs using freely available code (http://sites.google.com/site/honcheongso/software/total-vg)40,41. As the correction for winners curse may be influenced by asymmetry in the distribution of t (arising from the choice of reference allele) we bootstrapped the choice of reference allele (5,000 iterations) to derive the median value and 95% confidence intervals of the estimates of variance explained (Extended Data Fig. 11b, c). The correction for winner’s curse corrected for upward biases when estimating the percentage variance explained by each SNP across the genome via simulation40, but this correction could still allow some bias. Future large studies will be able to evaluate independently the percentage variance explained.
