probTDT: TDT on genotype probabilities matrix

Description

Computes the genotypic TDT for a a matrix representing SNP genotype probabilities.

Usage

probTDT(mat.geno, model = c("additive", "dominant", "recessive"),  size = 50)

Arguments

mat.geno

a numeric matrix with one row for each SNP and $9 * t$ columns representing genotype probabilities for $t$ trios. Each of the $t$ blocks (i.e. snp[1:9], snp[10:18], ...) must consist of sets of the three genotype probabilities for AA, AB and BB calls, of father, mother, and offspring (in this order), as would be output by BEAGLE, for example. The genotype probabilities must sum to 1 (up to slight imprecision) in each individual. Missing values are allowed and need to be coded by NA. Note that the order of the columns is not checked to be in terms of minor allele -- any dominant or recessive tests are for allele B, as ordered in the mat.geno, not necessarily for the minor allele.

model

type of model that should be fitted. Abbreviations are allowed. Thus, e.g., model = "dom" will fit a dominant model, and model = "r" an recessive model. See description of mat.geno for a caveat about allele ordering.

size

the number of SNPs considered simultaneously when computing the parameter estimates. Ignored if fast = FALSE.

...

ignored.

Value

coef: the estimated parameter,
se: the estimated standard deviation of the parameter estimate,
stat: Wald statistic,
RR: the relative risk, i.e.\ for trio data, exp(coef) (see Schaid, 1996),
lowerRR: the lower bound of the 95% confidence interval for RR,
upperRR: the upper bound of the 95% confidence interval for RR,
usedTrios: the number of trios affecting the parameter estimation,
pMendelErr: the sum across families of probabilities of Mendelian errors,
...: further internal parameters

References

Schaid, D.J. (1996). General Score Tests for Associations of Genetic Markers with Disease Using Cases and Their Parents. Genetic Epidemiology, 13, 423-449.

Schwender, H., Taub, M.A., Beaty, T.H., Marazita, M.L., and Ruczinski, I. (2011). Rapid Testing of SNPs and Gene-Environment Interactions in Case-Parent Trio Data Based on Exact Analytic Parameter Estimation. Biometrics, 68, 766-773.

Taub M.A., Schwender H., Beatty T.H., Louis T.A., Ruczinski I. (2012). Incorporating genotype uncertainties into the genotypic TDT for main effects and gene-environment interactions. Genetic Epidemiology, 36, 225-234.

Examples

Run this code

# Load the simulated data.
data(trio.data)

# All SNPs in prob.mat.test can be tested by
prob.tdt.out <- probTDT(prob.mat.test)

# By default, an additive mode of inheritance is considered.
# If another mode, e.g., the dominant mode, should be 
# considered, then this can be done by
prob.tdt.out2 <- probTDT(prob.mat.test, model = "dominant")

# By default, statistics for the top 5 SNPs are displayed.
# If another number of SNPs, say 10, should be displayed,
# then this can be done by
print(prob.tdt.out2, top = 10)

# The statistics for all SNPs (not ordered by their 
# significance) can be obtained by
print(prob.tdt.out2, top = 0)