MFMextra

This R package provides the simulation functions used to assess the joint fine-mapping methods of MFM.

Website available at: https://jennasimit.github.io/MFMextra/

Installation

install.packages("devtools") # if you don't already have the package
library(devtools)
install_github("jennasimit/MFMextra")

Simulation of case-control data for one disease

Below is an example of how to use hapgen2 to simulate N0 cases and N1 controls in a gene (IL2RA) on chromosome 10, where we set two causal variants. The positions of the causal variants are $c1 and $c2, which have $ORhet1 and $ORhet2 as the respective odds ratios relating the odds of disease in heterozygote carriers of the non-reference allele (this is specified by the ‘1’ following each of $c1 and $c2; ‘0’ indicates with respect to the reference allele) compared to the homozygote reference allele. We assume a multiplicative model so that OR for homozygote disease risk is OR^2. For each simulation the causal variants were randomly selected from a certain SNP group.

This requires map, legend and hap files, which could be obtained from a reference panel (e.g. CEU of 1000 Genomes vcf file by using vcftools with the –IMPUTE option. To output only a subset of SNPs, we specify the SNP positions, line-by-line, in the file keep-snps.txt.

ORhom1=$(bc -l <<< "$ORhet1 ^2")
ORhom2=$(bc -l <<< "$ORhet2 ^2")

./hapgen2 \
-m ./genetic_map_chr10_combined_b37.txt #map file \
-l ./IL2RA.impute.legend # legend file \
-h ./IL2RA.impute.hap # hap file \
-n $N0 $N1 # N0 controls, N1 cases \
-dl $c1 1 $ORhet1 $ORhom1 $c2 1 $ORhet2 $ORhom2 \
-no_haps_output -no_gens_output \
-t ./keep-snps.txt  # output for subset of SNPs that are listed in this file \
-Ne 11418 # effective population size; 11418 recommended for CEU \
-o ./CCdata  # prefix of output files

Simulation of null data that forms the basis for simulating a specific region for two diseases with shared controls

Below is an example of how to use hapgen2 to simulate 100,000 individuals with no associated SNPs in a gene (IL2RA) on chromosome 10. This requires map, legend and hap files, which could be obtained from a reference panel (e.g. CEU of 1000 Genomes vcf file by using vcftools with the –IMPUTE option. By not specifying the causal variants, the default is to simulate null data. To output only a subset of SNPs, we specify the SNP positions, line-by-line, in the file keep-snps.txt.

./hapgen2 \
-m ./genetic_map_chr10_combined_b37.txt #map file \
-l ./IL2RA.impute.legend # legend file \
-h ./IL2RA.impute.hap # hap file \
-n 100000 0 # 100,000 controls, 0 cases \
-no_haps_output -no_gens_output \
-t ./keep-snps.txt  # output for subset of SNPs that are listed in this file \
-Ne 11418 # effective population size; 11418 recommended for CEU \
-o ./null_100k  # prefix of output files

Run the following to generate the MFMextra website:

Rscript -e "pkgdown::build_site()"