mrMLM v4.0.2: An R Platform for Multi-locus Genome-wide Association Studies

Abstract

Previous studies have reported that some important loci are missed in single-locus genome-wide association studies (GWAS), especially because of the large phenotypic error in field experiments. To solve this issue, multi-locus GWAS methods have been recommended. However, only a few software packages for multi-locus GWAS are available. Therefore, we developed an R software named mrMLM v4.0.2. This software integrates mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB, and ISIS EM-BLASSO methods developed by our lab. There are four components in mrMLM v4.0.2, including dataset input, parameter setting, software running, and result output. The fread function in data.table is used to quickly read datasets, especially big datasets, and the doParallel package is used to conduct parallel computation using multiple CPUs. In addition, the graphical user interface software mrMLM.GUI v4.0.2, built upon Shiny, is also available. To confirm the correctness of the aforementioned programs, all the methods in mrMLM v4.0.2 and three widely-used methods were used to analyze real and simulated datasets. The results confirm the superior performance of mrMLM v4.0.2 to other methods currently available. False positive rates are effectively controlled, albeit with a less stringent significance threshold. mrMLM v4.0.2 is publicly available at BioCode (https://bigd.big.ac.cn/biocode/tools/BT007077) or R (https://cran.r-project.org/web/packages/mrMLM.GUI/index.html) as an open-source software.

Keywords: Genome-wide association study; Linear mixed model; Multi-locus genetic model; R; mrMLM.

Figure 1

The framework of mrMLM v4.0.2

Figure 2

Performance of mrMLM v4.0.2 in detecting QTNs for rice grain width The dataset was derived from the reference . QTN, quantitative trait nucleotide; GWAS, genome-wide association study.

Figure 3

Manhattan and QQ plots for grain width, oil concentration, and kidney weight in GWAS using mrMLM v4.0.2 Left is Manhattan plot, while right is QQ plot. A. Grain width in rice . B. Oil concentration in maize . C. Kidney weight in Simmental beef cattle . The dots were used to indicate the known genes detected both by mrMLM and in original studies (black), only by the software mrMLM (red), and only in original studies (grey), as well as candidate genes around QTNs from the software mrMLM (blue). QQ, quantile–quantile.