BLINK: A Package for Next Level of Genome Wide Association Studies with Both Individuals and Markers in Millions

Abstract

Big data, accumulated from biomedical and agronomic studies, provides the potential to identify genes controlling complex human diseases and agriculturally important traits through genome-wide association studies (GWAS). However, big data also leads to extreme computational challenges, especially when sophisticated statistical models are employed to simultaneously reduce false positives and false negatives. The newly developed Fixed and random model Circulating Probability Unification (FarmCPU) method uses a bin method under the assumption that Quantitative Trait Nucleotides (QTNs) are evenly distributed throughout the genome. The estimated QTNs are used to separate a mixed linear model into a computationally efficient fixed effect model (FEM) and a computationally expensive random effect model (REM), which are then used iteratively. To completely eliminate the computationally expensive REM, we replaced REM with FEM by using Bayesian information criteria. To eliminate the requirement that QTNs be evenly distributed throughout the genome, we replaced the bin method with linkage disequilibrium information. The new method is called Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). Both real and simulated data analyses demonstrated that BLINK improves statistical power compared to FarmCPU, in addition to a remarkable improvement in computing time. Now, a dataset with half million markers and one million individuals can be analyzed within five hours, compared with one week using FarmCPU.