trio.sim: Simulate Case-Parent Trios
In trio: Testing of SNPs and SNP Interactions in Case-Parent Trio Studies

Description Usage Arguments Details Value Author(s) References See Also Examples

trio.sim generates case-parents trios when the disease risk of children is specified by (possibly higher-order) SNP-SNP interactions. The SNP minor allele frequencies and/or haplotypes are specified by the user, as are the parameters in the logistic model that describes the disease risk. If pi.usr is specified, a specific type of model, namely the well-known Risch model, will be employed.

1 2	trio.sim(freq, interaction = "1R and 2D", prev = 1e-3, OR = 1, pi.usr = 0, n = 100, rep = 1, step.save = NULL, step.load = NULL, verbose = FALSE)

`freq`	A data frame specifying haplotype blocks and frequencies. For an example, see the data frame `simuBkMap` contained in this package. If provided, the following argument `blocks` will be ignored. The object must have three columns in the following order: block identifiers (`key`), haplotypes (`hap`), and haplotype frequencies (`freq`). The block identifiers must be unique for each block. For each block, the haplotypes must be encoded as a string of the integers 1 and 2, where 1 refers to the major allele and 2 refers to the minor allele. The respective haplotype frequencies will be normalized to sum one.
`interaction`	A string that specifies the risk altering genotype interaction as a Boolean term, such as "7D or 19R", or "(not 10D) or 45D". Each locus can appear at most once in the string, and the the Boolean term not can appear at most once before each locus, and must be enclosed in parenthesis, e.g., "(not 3D)". Therefore, strings such as "not (not 3D)" and "not 3D or 5R" are prohibited. Parenthesis are also used to unambiguously define the Boolean expression as a binary tree, i.e., every parent node has exact two children. For example Thus, a long string such as "1R or 3D or 5R" must be written as "(1R or 3D) or 5R" or as "1R or (3D or 5R)", even though the parenthesis are technically redundant. There is also a limit on the size of the interactions, please see Details below.
`prev`	The prevalence of the disease in the simulated population among non-carriers (the "un-exposed" group).
`OR`	The odds ratio of disease in the simulated population, comparing carriers to non-carriers.
`pi.usr`	probability for an individual without the `interaction` to be affected
`n`	The number of case-parent trios simulated. The default is 100.
`rep`	The number of data set replicates generated. The default is 1.
`step.save`	The name of the binary file (without ".RData" extension) in which the object specifying the simulation mating tables and probabilities will be saved. The default value is `NULL` In that case, the object will not be saved for re-use in later run. See Details.
`step.load`	The name of an existing binary file (without ".RData" extension) in which the object specifying the simulation mating tables and probabilities have been saved (see above). The default value is `NULL`. In that case, a new object will be generated.
`verbose`	A logical value indicating whether or not to print information about memory and time usage.

The function trio.sim simulates case-parent trio data when the disease risk of children is specified by (possibly higher-order) SNP-SNP interactions. The mating tables and the respective sampling probabilities depend on the haplotype frequencies (or SNP minor allele frequencies when the SNP does not belong to a block). This information is specified in the freq argument of the function. The probability of disease is assumed to be described by the logistic term logit(p) = a + b I[Interaction], where a = logit (prev) and b = log(OR), with prev and OR specified by the user. Note that at this point only data for two risk groups (carriers versus non-carriers) can be simulated. Since the computational demands for generating the mating is dependent on the number of loci involved in the interactions and the lengths of the LD blocks that contain these disease loci, the interaction term can only consist of up to six loci, not more than one of those loci per block, and haplotype (block) lengths of at most 5 loci.

Generating the mating tables and the respective sampling probabilities necessary to simulate case-parent trios can be very time consuming for interaction models involving three or more SNPs. In simulation studies, many replicates of similar data are usually required, and generating these sampling probabilities in each instance would be a large and avoidable computational burden (CPU and memory). The sampling probabilities depend foremost on the interaction term and the underlying haplotype frequencies, and as long as these remain constant in the simulation study, the mating table information and the sampling probabilities can be "recycled". This is done by storing the relevant information (denoted as "step-stone") as a binary R file in the working directory (using the argument step.save), and loading the binary file again in future simulations (using the argument step.load), speeding up the simulation process dramatically. It is even possible to change the parameters prev and OR (corresponding to a and b in the logistic model) in these additional simulations, as the sampling probabilities can be adjusted accordingly.

A list of matrices, containing the simulated data sets, in genotype format (indicating the number of variant alleles), including family and subject identifiers.

Qing Li, mail2qing@yahoo.com

Li, Q., Fallin, M.D., Louis, T.A., Lasseter, V.K., McGrath, J.A., Avramopoulos, D., Wolyniec, P.S., Valle, D., Liang, K.Y., Pulver, A.E., and Ruczinski, I. (2010). Detection of SNP-SNP Interactions in Trios of Parents with Schizophrenic Children. Genetic Epidemiology, 34, 396-406.

trio.prepare

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data(trio.data)
sim <- trio.sim(freq=simuBkMap, interaction="1R and 5R", prev=.001, OR=2, n=20, rep=1)
sim[[1]][1:6, 1:12]

     famid pid snp1 snp2 snp3 snp4 snp5 snp6 snp7 snp8 snp9 snp10
[1,]     1   1    0    0    0    0    0    1    0    1    1     1
[2,]     1   2    0    0    0    0    0    1    1    1    1     1
[3,]     1   3    0    0    0    0    0    2    0    0    0     2
[4,]     2   1    0    1    1    1    1    1    0    0    1     2
[5,]     2   2    0    0    1    1    1    1    0    0    0     2
[6,]     2   3    0    1    1    1    1    0    0    0    1     2