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:

1. 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

2. 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 TDTDC, 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 TDTDC test.
Z.TDT.DplusC	2-df χ2-distributed test statistic for TDTD+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 TDTD+C test.

Notes

1. 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/).