TriadSim {TriadSim}

Simulation main function

Description

TriadSim can simulate genotypes for case-parent triads, case-control, and quantitative trait samples with realistic linkage diequilibrium structure and allele frequency distribution. For studies of epistasis one can simulate models that involve specific SNPs at specific sets of loci, which we will refer to as "pathways". TriadSim generates genotype data by resampling triad genotypes from existing data. It takes genotypes in PLINK format as the input files.

Usage

TriadSim(
  input.plink.file,
  out.put.file,
  fr.desire,
  pathways,
  n.ped,
  N.brk,
  target.snp = NA,
  P0,
  is.OR,
  risk.exposure,
  risk.pathway.unexposed,
  risk.pathway.exposed,
  is.case = TRUE,
  e.fr = NA,
  pop1.frac = NA,
  P0.ratio = 1,
  rcmb.rate = NA,
  no_cores = NA,
  qtl = FALSE,
  same.brk = FALSE,
  flip = TRUE
)

Arguments

input.plink.file

gives the filenames (as well as the path) of the source data used for resampling. The input files are in PLINK format. For simulations of a homogenous population, it is a vector of three character strings for the base filenames of the mother's father's and child's PLINK files. The PLINK files are in bed format and three files with extensions .bed .bim and .fam are expected for each individual's genotypes. The mothers, fathers, and children must be from the same set of triad families even though the ordering of the families can be different for the three sets of data. For simulations under population stratification it is a list of two vectors. Each vector is a vector of three character strings giving the base filenames for the PLINK files as described above.The two vectors correspond to the two subpopulations.

out.put.file

is a character string giving the pathway to and the base filename of the output file. The names of the final output files also contain information on chromosome number. E.g., for a base filename "trio" and for chromosome 1 the final filenames for the PLILK files are "trio1.bim","trio1.bed" and "trio1.fam".

fr.desire

is a double number giving the desired frequency of the target SNPs.

pathways

is a list of vectors of integers. Each vector of integers denotes the SNPs involved in a particular pathway. E.g. list(1:4,5:8)

n.ped

is an integer giving the number of trios to be simulated

N.brk

is an integer giving the number of breaks to be picked for each chromosome.

target.snp

is a vector of integers showing the row number of the target SNPs in the .bim file.

P0

gives the baseline disease prevalence in the unexposed individuals with 0 copies of the risk pathways.

is.OR

is a boolean varialbe denoting wether the input risk parameters are odds ratios. It is TRUE when the input risks are odds ratios.

risk.exposure

is a double giving the relative risk (or odds ratio, if is.OR=TRUE) of the exposure main effect.

risk.pathway.unexposed

is a vector of doubles giving the relative risk (or odds ratio, if is.OR=TRUE) of each risk pathways in the unexposed individuals with the risk of unexposed individuals who carry no copies of the pathways as a reference.For scenarios that do not involve exposure the value of this vector is for all individuals.

risk.pathway.exposed

is a vector of doubles giving the relative risk (or odds ratio, if is.OR=TRUE) of each risk pathways in the exposed individuals. with the risk of exposed individuals who carry no copies of the pathways as a reference. For scenarios that do not involve exposure the value of this vector is not used.

is.case

is a boolean variable. When is.case = TRUE case-parents trios will be simulated.Otherwise, control-parents trios will be simulated.

e.fr

is a double number between 0 and 1 which gives the exposure prevalence.

pop1.frac

is a double number between 0 and 1 which gives the fraction of population 1 for a population stratification scenario.

P0.ratio

gives the ratio of the baseline disease prevalence in the second subpopulation to that of the first subpopulation.

rcmb.rate

the default value is NA. rcmb.rate is a dataframe containing the recombination rates at each SNP. The ordering of the SNPs (in rows) should be identical to that of snp.all2. It has 4 columns with the column names 'CHR','RS','POS', and 'RATE' representing "the chromosomal number", "SNP rs number", "chromosomal position", and "recombination rate", respectively. The recombination rate represents the maximum recombination rate in the chromosomal region between the current SNP and the SNP above (or the first basepair of the chromosome for the first SNP on a chromosome).When no rcmb.rate is provided the function will pick the breaking points randomly.

no_cores

is an integer which specifies the number of CPU cores to parallelized.contain values

qtl

is a boolean variable denoting whether a quantitative trait (qtl=TRUE) or a binary trait (qtl=FALSE) is to be simulated. For a binary trait only affected families will be kept. The default value is qtl=FALSE.

same.brk

is an indicator variable to denote whether the same set of breaking points will be used for all simulated triads. The default value is FALSE.

flip

is an indicator variable denoting whether the mother's and the father's genotypes will be swapped to wipe out potential maternal effects in the orignal data. The default value is TRUE.

Value

this function simulates genotypes of parent-offspring triads and writes PLINK files into the designated directory. Genotypes on each chromosome will be written into a separate set of PLINK files. In each set of PLINK files genotypes of the mothers, fathers, and children are stacked on top of each other. The first third of the rows are genotypes of the mothers'.The seond third are those of the fathers' and the last third are those of the children's. The following files are also generated under specific scenarios: a file with name ending with "exp.txt" containing the exposure data when exposure is involved in the risk model. a file with name ending with "pop.txt" containing information on subpopulation membership when the simulation involves a stratified scenario. a file with name ending with "pheno.tx" containing quantitative trait phenotype when a quantitative trait is involved.

Examples

m.file <- file.path(system.file(package = "TriadSim"),'extdata/pop1_4chr_mom')
f.file <- file.path(system.file(package = "TriadSim"),'extdata/pop1_4chr_dad')
k.file <- file.path(system.file(package = "TriadSim"),'extdata/pop1_4chr_kid')
input.plink.file <- c(m.file, f.file, k.file)
## Not run: TriadSim(input.plink.file, file.path(tempdir(),'triad'), fr.desire=0.05,pathways=list(1:4,5:8),
       n.ped=1000, N.brk=3, target.snp=NA,P0=0.001,is.OR=FALSE,risk.exposure= 1,
       risk.pathway.unexposed=c(1.5, 2), risk.pathway.exposed=c(1.5, 2), is.case=TRUE, e.fr=NA, 
       pop1.frac=NA, P0.ratio=1, rcmb.rate, no_cores=1)
## End(Not run)