MRPEA Files

Genome-wide association studies (GWAS) based pathway association analysis is a powerful approach for the genetic studies of human complex diseases. However, the genetic confounding effects of genes affecting environment exposure risks, can decrease the accuracy of GWAS-based pathway association analysis. In this study, we developed a pathway association analysis approach MRPEA, which was capable of correcting the genetic confounding effects of environmental exposures related genes, utilizing the GWAS summary data of environmental exposures.

1.Installing and Running MRPEA
MRPEA is developed by C to interface with R for efficient data analysis. Please make sure that R (http://www.r-project.org/) has been installed on your system. MRPEA is a command line based program. Unzip the downloaded "MRPEA" package and run "MRPEA" program at your terminal window to start analysis.  
Example:
./MRPEA

2.Parameter Setting
MRPEA will ask users to input a set of parameters before starting analysis:
[1]GWAS summary file name of target disease: Please input the storage path and name of GWAS summary data file of target disease. 
[2]Type of association testing parameter of target disease: MRPEA provides two choices for GWAS summary data, including: 
(1) BETA: regression coefficient for quantitative trait; 
(2) OR: odds ratio for qualitative trait. 
[3]GWAS summary file name of environmental exposure: Please input the storage path and name of GWAS summary data file of environmental exposure. 
[4]Type of association testing parameter of environmental exposure: MRPEA provides two choices for GWAS summary data, including: 
(1) BETA: regression coefficient for quantitative trait; 
(2) OR: odds ratio for qualitative trait. 
[5]SNP weighting parameter file name: Please input the storage path and name of SNP weighting parameter Wg file. Wg be calculated by sample size weighting and inverse variance weighting approaches.
[6]SNP-gene annotation file name: Please input the storage path and name of SNP-gene annotation file.   
[7]Gene-pathway annotation file name: Please input the storage path and name of gene-pathway annotation file. Users can obtain pathway annotation information from public database, such as Gene Ontology (http://www.geneontology.org), GSEA Molecular Signatures Database (http://www.broadinstitute.org/gsea/ msigdb/index.jsp), Reactome (http://www.reactome.org/). 
[8]Permuation times: Permutations are used for P value calculation in MRPEA. More than 1,000 permutations are recommended for obtaining accurate P values. Note, too large permutation times will make MRPEA taking a long time to complete data analysis.
[9]Max and min sizes of analyzed pathways: Users need to define the maximum (fault value = 200 genes) and minimum (fault value = 5 genes) sizes of pathways analyzed by MRPEA. 
[10]Exponentially weighting parameter of GWAS statistics of target disease: Please input the weighting parameters Ug (fault value = 1) of GWAS statistics of target disease.  
[11]Exponentially weighting parameter of GWAS statistics of environmental exposure: Please input the weighting parameters Ue (fault value = 1) of GWAS statistics of environmental exposure.  

3.Output files
MRPEA will output two result files:
[1]Pathway_result.txt: Pathway analysis result files. Each line of this file records a pathway and corresponding analysis results.
The pathways with FDR < 0.05 are considered as significant pathways. 
[2]Plot.pdf: Plots of pathway analysis results of MRPEA. In generated figures, each point denotes a pathway. X-axis presents the total number of pathways analyzed by MRPEA software. Y-axis shows -log10 (P values) calculated by MRPEA.