Reliable heritability estimation using sparse regularization in ultrahigh dimensional genome-wide association studies

BACKGROUND: Data from genome-wide association studies (GWASs) have been used to estimate the heritability of human complex traits in recent years. Existing methods are based on the linear mixed model, with the assumption that the genetic effects are random variables, which is opposite to the fixed effect assumption embedded in the framework of quantitative genetics theory. Moreover, heritability estimators provided by existing methods may have large standard errors, which calls for the development of reliable and accurate methods to estimate heritability. RESULTS: In this paper, we first investigate the influences of the fixed and random effect assumption on heritability estimation, and prove that these two assumptions are equivalent under mild conditions in the theoretical aspect. Second, we propose a two-stage strategy by first performing sparse regularization via cross-validated elastic net, and then applying variance estimation methods to construct reliable heritability estimations. Results on both simulated data and real data show that our strategy achieves a considerable reduction in the standard error while reserving the accuracy. CONCLUSIONS: The proposed strategy allows for a reliable and accurate heritability estimation using GWAS data. It shows the promising future that reliable estimations can still be obtained with even a relatively restricted sample size, and should be especially useful for large-scale heritability analyses in the genomics era. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2792-7) contains supplementary material, which is available to authorized users.