An Extended Application of the Fast Multi-Locus Ridge Regression Algorithm in Genome-Wide Association Studies of Categorical Phenotypes

Abstract

Categorical (either binary or ordinal) quantitative traits are widely observed to measure count and resistance in plants. Unlike continuous traits, categorical traits often provide less detailed insights into genetic variation and possess a more complex underlying genetic architecture, which presents additional challenges for their genome-wide association studies. Meanwhile, methods designed for binary or continuous phenotypes are commonly used to inappropriately analyze ordinal traits, which leads to the loss of original phenotype information and the detection power of quantitative trait nucleotides (QTN). To address these issues, fast multi-locus ridge regression (FastRR), which was originally designed for continuous traits, is used to directly analyze binary or ordinal traits in this study. FastRR includes three stages of continuous transformation, variable reduction, and parameter estimation, and it can computationally handle categorical phenotype data instead of link functions introduced or methods inappropriately used. A series of simulation studies demonstrate that, compared with four other continuous or binary or ordinal approaches, including logistic regression, FarmCPU, FaST-LMM, and POLMM, the FastRR method outperforms in the detection of small-effect QTN, accuracy of estimated effect, and computation speed. We applied FastRR to 14 binary or ordinal phenotypes in the Arabidopsis real dataset and identified 479 significant loci and 76 known genes, at least seven times as many as detected by other algorithms. These findings underscore the potential of FastRR as a very useful tool for genome-wide association studies and novel gene mining of binary and ordinal traits.