GDT is a software package including a variety of family-based genomewide association (GWA) tests. The main method GDT tests within-family association by examining differences of genotypes from all discordant relative pairs. The GDT method generalizes family-based association tests, in the sense that it extends methods such as TDT, 1-TDT, and PDT.
GENERAL INPUT FILESThe input files include at least a data file, a pedigree file, and a map file. They can be specified with the -d, -p, and -m parameters. The command line will look like this:
prompt> gdt -d ex.dat -p ex.ped -m ex.map --gdtGDT supports input files in LINKAGE, GENEHUNTER, and MERLIN format. Please read MERLIN tutorial for details of MERLIN input files.
Examples of association tests are:
prompt> gdt -d ex.dat -p ex.ped -m ex.map --stop 3 --cov sex --gdtThe output may look like this:
Binary Trait Association : --TDT, --oneTDT, --PDT
Quasi-likelihood Methods : --WQLS, --MQLS, --GEE1
GDT & Extensions : --GDT [ON], --poGDT
Quantitative Association : --fastAssoc, --robustAssoc
Haplotype Analysis : --hapfile []
Linkage Analysis : --ibdfile []
Model Parameters : --trait [], --covariate [sex]
Analysis Parameters : --prevalence
Positions : --start, --stop [3.00], --SNP []
Output : --prefix [GDT]
Fitted Polygenic Models (GEE)
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Trait N Mean sex
T1D 11674 -0.071 -0.151
(se) 0.019 0.032
Phenotype: T1D [GDT] (2496 families)
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Marker Position Pair Allele Freq Delta Z_GDT pvalue
rs741737 0.000000 10304 2 0.258 0.005 0.728 0.47
rs7481525 0.000050 9524 2 0.402 0.004 0.411 0.68
rs1105350 0.730000 4015 2 0.435 0.009 0.851 0.4
rs2029463 1.050000 10350 1 0.127 0.007 1.195 0.23
rs1004446 2.100000 10347 2 0.690 0.053 6.292 3.1E-10
In the above example, all markers with position < 3Mb are tested for association using the GDT method adjusting for SEX. There are 8
columns in the genome scan output: marker's name, marker's position, number of discordant relative pairs, the
reference allele, frequency of the reference allele, allele frequency difference between cases and controls,
the Z statistic, and P value.
All tests implemented in the current version include:
--TDT: the Transmission/Disequilibrium Test (Spielman et al. 1993)
--oneTDT: or 1-TDT, a TDT extension that allows one parent data (Sun et al. 1999)
--PDT: Pedigree Disequilibrium Test (Martin et al. 2001, 2002)
--MQLS: MQLS, more powerful Quasi-Likelihood Score
method (Thornton and McPeek 2007)
--WQLS: WQLS (Bourgain et al. 2003)
--GEE1: a generalized estimating equations (GEE) implementataion assuming an independent working covariance (Liang and Zeger 1986)
--poGDT: a variation of GDT that only examines discordant
parent-offspring pairs (Chen et al. 2009 AJHG 85:364-376)
--GDT: Generalized Disequlibrium Test (Chen et al. 2009 AJHG 85:364-376)
Methods implemented include:
--fastAssoc: the score test (Chen and Abecasis 2007)
--robustAssoc: robust score test (Chen et al. 2009 AJHG 85:364-376)
--trait trait_names specifies one or more traits to be analyzed. All
traits will be analyzed if not specified.
--covariate covariate_names specifies covariates to be included in the
model.E.g., --cov sex,age
--start position specifies a starting position for analysis
--stop position specifies a stopping position for analysis
--SNP SNP_names specifies a list of SNPs used in the analysis. E.g., --SNP SNP1,SNP2
REFERENCES
Chen WM, Manichaikul A, Rich SS (2009) A generalized family-based association test for dichotomized traits. Am J Hum Genet 85:364-376 [PDF] Chen WM, Abecasis GR (2007) Family-based association tests for genomewide association scans. Am J Hum Genetc81:913-926 [PDF]
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Last updated: September 3, 2009 by Wei-Min Chen