RayDebashree/TDT-like-tests

Description

'TDT-like-tests' is intended to be a suite of R functions for implementing modified transmission disequilibrium tests (TDT) on hybrid designs (e.g., case-parent/control-parent trios).

Currently, it has one function TDT.DCtrios that implements two TDT-like-tests for case-parent/control-parent trio design. It is based on the statistical methods proposed in Deng & Chen (2001), and as used in Ray et al. (2022). Please refer/cite both articles if this function is used:

Deng, H.W. and Chen, W.M. (2001). "The power of the transmission disequilibrium test (TDT) with both case-parent and control-parent trios". Genetics Research, 78:289-302. https://doi.org/10.1017/s001667230100533x
Ray, D., Vergara, C., Taub, M.A., Wojcik, G., Ladd-Acosta, C., Beaty, T.H., and Duggal, P. (2022) "Benchmarking statistical methods for analyzing parent-child dyads in genetic association studies". Genetic Epidemiology. https://doi.org/10.1002/gepi.22453

Key Words: Case-parent/control-parent design; Family-based GWAS; Hybrid design; Offspring design; Transmission disequilibrium; Trios

Requirements

R (>= 3.0.1)

How to Install within R

require(devtools)
source_url("https://github.com/RayDebashree/TDT-like-tests/blob/main/TDT_DC_tests.R?raw=TRUE")

It is recommended to download/copy the stand-alone R program in this repository, save it in your local directory of choice and source() it from your local directory. When a new version of the program is available, older versions may be removed from this repository.

Usage

Simple example

TDT.DCtrios(Tcase, NTcase, Tcontrol, NTcontrol)

Arguments

Input	Description
`Tcase`	The number of times the marker allele is transmitted from a parent to an affected child. This relates to the TDT applied to case-parent trios only with at least one heterozygous parent.
`NTcase`	The number of times the marker allele is not transmitted from a parent to an affected child. This relates to the TDT applied to case-parent trios only with at least one heterozygous parent.
`Tcontrol`	The number of times the marker allele is transmitted from a parent to an unaffected child. This relates to the TDT applied to control-parent trios only with at least one heterozygous parent. This TDT can be viewed as a test for 'healthy' rather than 'disease' allele, though at the same disease susceptibility locus.
`NTcontrol`	The number of times the marker allele is not transmitted from a parent to an unaffected child. This relates to the TDT applied to control-parent trios only with at least one heterozygous parent.

Value

Output	Description
`Tcase`	Same as input above.
`NTcase`	Same as input above.
`Tcontrol`	Same as input above.
`NTcontrol`	Same as input above.
`Z.TDT.DC`	1-df χ²-distributed test statistic for TDT_DC, a contingency table test for association of disease status with allele transmissions from case- and control-parent trios considered jointly.
`pvalue.TDT.DC`	P-value of the 1-df TDT_DC test.
`Z.TDT.DplusC`	2-df χ²-distributed test statistic for TDT_D+C, a contingency table test for association of disease status with allele transmissions based on combining the independent TDT statistics from case-parent trios and from control-parent trios separately.
`pvalue.TDT.DplusC`	P-value of the 2-df TDT_D+C test.

Notes

To obtain T and NT values per variant for a specific family type (either case-parent trios or control-parent trios), one may implement --TDT option from the GDT software by Chen et al., 2009 (https://www.chen.kingrelatedness.com/software/GDT/).