Package ‘mrMLM’

August 26, 2018

Type Package
Title Multi-Locus Random-SNP-Effect Mixed Linear Model Tools for
Genome-Wide Association Study
Version 3.1
Date 2018-8-25
Author Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, and Zhang Yuan-Ming
Maintainer Yuanming Zhang<[email protected]>
Description Conduct multi-locus genome-wide association study under the framework of random-
SNP-effect mixed linear model (mrMLM). First, each marker on the genome is scanned. Bonfer-
roni correction is replaced by a less stringent selection criterion for signifi-
cant test. Then, all the markers that are potentially associated with the trait are included in a multi-
locus model, their effects are estimated by empirical Bayes and true QTN are identified by likeli-
hood ratio test. Wen YJ, Zhang H, Ni YL, Huang B, Zhang J, Feng JY, Wang SB, Dun-
well JM, Zhang YM, Wu R (2018) <doi:10.1093/bib/bbw145>.
Depends MASS,data.table,doParallel,foreach
Imports methods,openxlsx,stringr,qqman,ggplot2,lars,ncvreg,coin,sampling,bigmemory
License GPL (>= 2)
NeedsCompilation no
Repository CRAN
Date/Publication 2018-08-25 22:10:03 UTC

R topics documented:
DoData . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
FASTmrEMMA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
FASTmrMLM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Gen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
inputData . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
ISIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
mrMLM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
mrMLMFun . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Phe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

1
2 DoData

pKWmEB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
pLARmEB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
ReadData . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Index 13

DoData process raw data

Description

process raw data for later use

Usage

DoData(genRaw,Genformat,pheRaw1q,kkRaw,psmatrixRaw,trait,type)

Arguments

genRaw raw genotype matrix.

Genformat genotype format.
pheRaw1q raw phenotype matrix.
kkRaw raw kinship matrix.
psmatrixRaw raw population structure matrix.
trait which trait to analysis.
type which type to transform.

Author(s)

Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming

Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
result=DoData(readraw$genRaw,Genformat=3,readraw$pheRaw1q,readraw$kkRaw,
readraw$psmatrixRaw,trait=1,type=2)
FASTmrEMMA 3

FASTmrEMMA To perform GWAS with FASTmrEMMA method

Description
FAST multi-locus random-SNP-effect EMMA

Usage
FASTmrEMMA(gen,phe,outATCG,genRaw,kk,psmatrix,svpal,svmlod,Genformat,Likelihood,CLO)

Arguments
gen genotype matrix.
phe phenotype matrix.
outATCG genotype for code 1.
genRaw raw genotype.
kk kinship matrix.
psmatrix population structure matrix.
svpal Critical P-value for selecting variable.
svmlod Critical LOD score for significant QTN.
Genformat Format for genotypic codes.
Likelihood restricted maximum likelihood (REML) and maximum likelihood (ML).
CLO number of CPU.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
InputData=inputData(readraw=Readraw,Genformat=1,method="FASTmrEMMA",trait=1)
result=FASTmrEMMA(InputData$doFME$gen,InputData$doFME$phe,
InputData$doFME$outATCG,InputData$doFME$genRaw,
InputData$doFME$kk,InputData$doFME$psmatrix,0.005,
svmlod=3,Genformat=1,Likelihood="REML",CLO=1)
4 FASTmrMLM

FASTmrMLM To perform GWAS with FASTmrMLM method

Description
FAST multi-locus random-SNP-effect Mixed Linear Model

Usage
FASTmrMLM(gen,phe,outATCG,genRaw,kk,psmatrix,svpal,svrad,svmlod,Genformat,CLO)

Arguments
gen genotype matrix.
phe phenotype matrix.
outATCG genotype for code 1.
genRaw raw genotype.
kk kinship matrix.
psmatrix population structure matrix.
svpal Critical P-value for selecting variable.
svrad Search Radius in search of potentially associated QTN.
svmlod Critical LOD score for significant QTN.
Genformat Format for genotypic codes.
CLO number of CPU.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
InputData=inputData(readraw=Readraw,Genformat=1,method="FASTmrMLM",trait=1)
result=FASTmrMLM(InputData$doMR$gen,InputData$doMR$phe,
InputData$doMR$outATCG,InputData$doMR$genRaw,
InputData$doMR$kk,InputData$doMR$psmatrix,0.01,svrad=20,
svmlod=3,Genformat=1,CLO=1)
Gen 5

Gen Genotype data

Description
Numeric format of genotype dataset.

Usage
data(Gen)

Details
Dataset input of Genotype for mrMLM function.

Author(s)
Maintainer: Yuan-Ming Zhang<[email protected]>

inputData Input data which have been transformed

Description
Input all the dataset which have been transformed

Usage
inputData(readraw,Genformat,method,trait)

Arguments
readraw genotype matrix.
Genformat genotype format.
method which method to analysis.
trait which trait to analysis.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>
6 ISIS

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
result=inputData(readraw=Readraw,Genformat=3,method="mrMLM",trait=1)

ISIS To perform GWAS with ISIS EM-BLASSO method

Description
Iterative Sure Independence Screening EM-Bayesian LASSO

Usage
ISIS(gen,phe,outATCG,genRaw,kk,psmatrix,svpal,svmlod,Genformat,CLO)

Arguments
gen genotype matrix.
phe phenotype matrix.
outATCG genotype for code 1.
genRaw raw genotype.
kk kinship matrix.
psmatrix population structure matrix.
svpal Critical P-value for selecting variable.
svmlod Critical LOD score for significant QTN.
Genformat Format for genotypic codes.
CLO number of CPU.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
InputData=inputData(readraw=Readraw,Genformat=1,method="ISIS EM-BLASSO",
trait=1)
result=ISIS(InputData$doMR$gen,InputData$doMR$phe,InputData$doMR$outATCG,
InputData$doMR$genRaw,InputData$doMR$kk,InputData$doMR$psmatrix,
0.01,svmlod=3,Genformat=1,CLO=1)
mrMLM 7

mrMLM Multi-Locus Random-SNP-Effect Mixed Linear Model Tools for

Genome-Wide Association Study

Description
Conduct multi-locus genome-wide association study under the framework of random-SNP-effect
mixed linear model (mrMLM). First, each marker on the genome is scanned. Bonferroni correction
is replaced by a less stringent selection criterion for significant test. Then, all the markers that are
potentially associated with the trait are included in a multi-locus model, their effects are estimated
by empirical Bayes and true QTNs are identified by likelihood ratio test.

Usage
mrMLM(fileGen,filePhe,fileKin,filePS,Genformat,method,Likelihood,trait,
SearchRadius,CriLOD,SelectVariable,Bootstrap,DrawPlot,Plotformat,Resolution,dir)

Arguments
fileGen File path and name in your computer of Genotype.
filePhe File path and name in your computer of Phenotype.
fileKin File path and name in your computer of Kinship.
filePS File path and name in your computer of Population Structure.
Genformat Format for genotypic codes, Num (number), Cha (character) and Hmp (Hapmap).
method Six multi-locus GWAS methods. Users may select one to six methods, includ-
ing mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB and ISIS
EM-BLASSO.
Likelihood This parameter is only for FASTmrEMMA, including restricted maximum like-
lihood (REML) and maximum likelihood (ML).
trait Traits analyzed from number 1 to number 2.
SearchRadius This parameter is only for mrMLM and FASTmrMLM, indicating Search Ra-
dius in search of potentially associated QTN.
CriLOD Critical LOD score for significant QTN.
SelectVariable This parameter is only for pLARmEB. SelectVariable=50 indicates that 50 po-
tentially associated variables are selected from each chromosome. Users may
change this number in real data analysis in order to obtain the best results as
final results.
Bootstrap This parameter is only for pLARmEB, including FASLE and TRUE, Boot-
strap=FALSE indicates the analysis of only real dataset, Bootstrap=TRUE in-
dicates the analysis of both real dataset and four resampling datasets.
DrawPlot This parameter is for all the six methods, including FALSE and TRUE, Draw-
Plot=FALSE indicates no figure output, DrawPlot=TRUE indicates the output
of the Manhattan, QQ and LOD score against genome position figures.
8 mrMLMFun

Plotformat This parameter is for all the figure files, including *.jpeg, *.png, *.tiff and *.pdf.
Resolution This parameter is for all the figure files, including Low and High.
dir This parameter is for the save path.

Details

Package: mrMLM
Type: Package
Version: 3.1
Date: 2018-8-4
Depends: MASS,data.table,doParallel,foreach
Imports: methods,openxlsx,stringr,qqman,ggplot2,lars,ncvreg,coin
License: GPL version 2 or newer
LazyLoad: yes

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

References
Methodological implementation of mixed linear models in multi-locus genome-wide association
studies. Yang-Jun Wen,Hanwen Zhang,Yuan-Li Ni,Bo Huang,Jin Zhang,Jian-Ying Feng,Shi-Bo
Wang,Jim M.Dunwell,Yuan-Ming Zhang,Rongling Wu.

Examples
G1=data(Gen)
P1=data(Phe)
mrMLM(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS=NULL,Genformat="Num",
method=c("ISIS EM-BLASSO"),Likelihood="REML",trait=1:1,SearchRadius=20,
CriLOD=3,SelectVariable=50,Bootstrap=FALSE,
DrawPlot=FALSE,Plotformat="jpeg",Resolution="Low",dir=tempdir())

mrMLMFun To perform GWAS with mrMLM method

Description
multi-locus random-SNP-effect Mixed Linear Model
Phe 9

Usage
mrMLMFun(gen,phe,outATCG,genRaw,kk,psmatrix,svpal,svrad,svmlod,Genformat,CLO)

Arguments
gen genotype matrix.
phe phenotype matrix.
outATCG genotype for code 1.
genRaw raw genotype.
kk kinship matrix.
psmatrix population structure matrix.
svpal Critical P-value for selecting variable
svrad Search Radius in search of potentially associated QTN.
svmlod Critical LOD score for significant QTN.
Genformat Format for genotypic codes.
CLO number of CPU.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
InputData=inputData(readraw=Readraw,Genformat=1,method="mrMLM",trait=1)
result=mrMLMFun(InputData$doMR$gen,InputData$doMR$phe,InputData$doMR$outATCG,
InputData$doMR$genRaw,InputData$doMR$kk,InputData$doMR$psmatrix,
0.01,svrad=20,svmlod=3,Genformat=1,CLO=1)

Phe Phenotype dataset

Description
Phenotype dataset of multiple traits.

Usage
data(Phe)
10 pKWmEB

Details
Dataset input of phenotype in mrMLM function.

Author(s)
Maintainer: Yuan-Ming Zhang<[email protected]>

pKWmEB To perform GWAS with pKWmEB method

Description
Kruskal-Wallis test with empirical Bayes under polygenic background control

Usage
pKWmEB(gen,phe,outATCG,genRaw,kk,psmatrix,svpal,svmlod,Genformat,CLO)

Arguments
gen genotype matrix.
phe phenotype matrix.
outATCG genotype for code 1.
genRaw raw genotype.
kk kinship matrix.
psmatrix population structure matrix.
svpal Critical P-value for selecting variable.
svmlod Critical LOD score for significant QTN.
Genformat Format for genotypic codes.
CLO number of CPU.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
InputData=inputData(readraw=Readraw,Genformat=1,method="pKWmEB",trait=1)
result=pKWmEB(InputData$doMR$gen,InputData$doMR$phe,InputData$doMR$outATCG,
InputData$doMR$genRaw,InputData$doMR$kk,InputData$doMR$psmatrix,
0.05,svmlod=3,Genformat=1,CLO=1)
pLARmEB 11

pLARmEB To perform GWAS with pLARmEB method

Description
polygene-background-control-based least angle regression plus Empirical Bayes

Usage
pLARmEB(gen,phe,outATCG,genRaw,kk,psmatrix,CriLOD,lars1,Genformat,Bootstrap,CLO)

Arguments
gen genotype matrix.
phe phenotype matrix.
outATCG genotype for code 1.
genRaw raw genotype.
kk kinship matrix.
psmatrix population structure matrix.
CriLOD Critical LOD score for significant QTN.
lars1 No. of potentially associated variables selected by LARS.
Genformat Format for genotypic codes.
Bootstrap Bootstrap=FALSE indicates the analysis of only real dataset, Bootstrap=TRUE
indicates the analysis of both real dataset and four resampling datasets.
CLO number of CPU.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
Readraw=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
InputData=inputData(readraw=Readraw,Genformat=1,method="pLARmEB",trait=1)
result=pLARmEB(InputData$doMR$gen,InputData$doMR$phe,InputData$doMR$outATCG,
InputData$doMR$genRaw,InputData$doMR$kk,InputData$doMR$psmatrix,
CriLOD=3,lars1=50,Genformat=1,Bootstrap=FALSE,CLO=1)
12 ReadData

ReadData read raw data

Description
read raw data which have not been transformed

Usage
ReadData(fileGen,filePhe,fileKin,filePS,Genformat)

Arguments
fileGen genotype matrix.
filePhe phenotype matrix.
fileKin kinship matrix.
filePS population structure matrix.
Genformat genotype format.

Author(s)
Zhang Ya-Wen, Li Pei, Ren Wen-Long, Ni Yuan-Li, Zhang Yuan-Ming
Maintainer: Yuan-Ming Zhang<[email protected]>

Examples
G1=data(Gen)
P1=data(Phe)
result=ReadData(fileGen=Gen,filePhe=Phe,fileKin=NULL,filePS =NULL,
Genformat=1)
Index

∗Topic R
mrMLM, 7
∗Topic mrMLM
mrMLM, 7
∗Topic package
mrMLM, 7
∗Topic
mrMLM, 7
<phenotype> (Phe), 9

chrom (Gen), 5

DoData, 2

FASTmrEMMA, 3
FASTmrMLM, 4

Gen, 5

inputData, 5
ISIS, 6

mrMLM, 7
mrMLMFun, 8

Phe, 9
pKWmEB, 10
pLARmEB, 11
pos (Gen), 5

ReadData, 12
rs# (Gen), 5

trait1 (Phe), 9
trait2 (Phe), 9
trait3 (Phe), 9

13