Deshrinking ridge regression for genome-wide association studies.

Abstract

Genome-wide association studies (GWAS) are still the primary steps toward gene discovery. The urgency is more obvious in the big data era when GWAS are conducted simultaneously for thousand traits, e.g. transcriptomic and metabolomic traits. Efficient mixed model association (EMMA) and genome-wide efficient mixed model association (GEMMA) are the widely used methods for GWAS. An algorithm with high computational efficiency is badly needed. It is interesting to note that the test statistics of the ordinary ridge regression (ORR) have the same patterns across the genome as those obtained from the EMMA method. However, ORR has never been used for GWAS due to its severe shrinkage on the estimated effects and the test statistics. We introduce a degree of freedom for each marker effect obtained from ORR and use it to deshrink both the estimated effect and the standard error so that the Wald test of ORR is brought back to the same level as that of EMMA. The new method is called deshrinking ridge regression (DRR). By evaluating the methods under three different model sizes (small, medium and large), we demonstrate that DRR is more generalized for all model sizes than EMMA, which only works for medium and large models. Furthermore, DRR detect all markers in a simultaneous manner instead of scanning one marker at a time. As a result, the computational time complexity of DRR is much simpler than EMMA and about m (number of genetic variants) times simpler than that of GEMMA when the sample size is way smaller than the number of markers. shizhong.xu@ucr.edu. Supplementary data are available at Bioinformatics online.