SumVg: Total heritability explained by all variants in genome-wide association studies based on summary statistics with standard error estimates

Genome-wide association studies (GWAS) are commonly employed to study the genetic basis of complex traits and diseases, and a key question is how much heritability could be explained by all variants in GWAS. One widely used approach that relies on summary statistics only is LD score regression (LDSC), however the approach requires certain assumptions on the SNP effects (all SNPs contribute to heritability and each SNP contributes equal variance). More flexible modeling methods may be useful. We previously developed an approach recovering the true z-statistics from a set of observed z-statistics with an empirical Bayes approach, using only summary statistics. However, methods for standard error (SE) estimation are not available yet, limiting the interpretation of results and applicability of the approach. In this study we developed several resampling-based approaches to estimate the SE of SNP-based heritability, including two jackknife and three parametric bootstrap methods. Simulations showed that delete-d-jackknife and parametric bootstrap approaches provide good estimates of the SE. Particularly, the parametric bootstrap approaches yield the lowest root-mean-squared-error (RMSE) of the true SE. In addition, we applied our method to estimate SNP-based heritability of 12 immune-related traits (levels of cytokines and growth factors) to shed light on their genetic architecture. We also implemented the methods to compute the sum of heritability explained and the corresponding SE in an R package SumVg, available at https://github.com/lab-hcso/Estimating-SE-of-total-heritability/ . In conclusion, SumVg may provide a useful alternative tool for SNP heritability and SE estimates, which does not rely on distributional assumptions of SNP effects.