VT: VT: Variable Threshold

In AssotesteR: Statistical Tests for Genetic Association Studies

Description

The Variable Threshold (VT) test has been proposed by Price et al (2010) based on the assumption that the minor allele frequencies of the causal rare variants may be different from those nonfunctional rare variants, which, if true, can be utilized to improve the power of the corresponding pooled association tests. The idea behind this approach is that there exists some (unknown) threshold T for which variants with a minor allele frequency (MAF) below T are more likely to be functional than are variants with an MAF above T. VT works by finding the maximum z-score across all possible values for the threshold T.

Usage

  VT(y, X, maf = 0.05, perm = 100)

Arguments

y	numeric vector with phenotype status: 0=controls, 1=cases. No missing data allowed
X	numeric matrix or data frame with genotype data coded as 0, 1, 2. Missing data is allowed
maf	numeric value indicating the minor allele frequency threshold for rare variants (must be a positive number between 0 and 1, maf=0.05 by default)
perm	positive integer indicating the number of permutations (100 by default)

Details

There is no imputation for the missing data. Missing values are simply ignored in the computations.

Value

An object of class "assoctest", basically a list with the following elements:

vt.stat	vt statistic
perm.pval	permuted p-value
args	descriptive information with number of controls, cases, variants, and permutations
name	name of the statistic

Author(s)

Gaston Sanchez

References

Price AL, Kryukov GV, de Bakker PIW, Purcell SM, Staples J, Wei LJ, Sunyaev SR (2010) Pooled Association Tests for Rare Variants in Exon-Sequencing Studies. The American Journal of Human Genetics, 86: 832-838

See Also

WSS

Examples

  ## Not run: 
  
  # number of cases
  cases = 500

  # number of controls
  controls = 500

  # total (cases + controls)
  total = cases + controls

  #  phenotype vector
  phenotype = c(rep(1, cases), rep(0, controls))

  # genotype matrix with 10 variants (random data)
  set.seed(1234)  
  genotype = matrix(rbinom(total*10, 2, 0.051), nrow=total, ncol=10)

  # apply VT with maf=0.05 and 500 permutations
  myvt = VT(phenotype, genotype, maf=0.05, perm=500)
  myvt
  
## End(Not run)

Example output

Loading required package: mvtnorm

 	 VT: Variable Threshold 

Info: 
   cases  controls  variants       maf   n.perms  
   5e+02     5e+02     1e+01     5e-02     5e+02  

  vt.stat   perm.pval   
 0.195815    0.716000   

AssotesteR documentation built on May 2, 2019, 3:55 a.m.