Produces an object of class haplinTDT, which is the result of
Transmission disequilibrium tests of data.
haplinTDT(filename, nsim.perm = 0, select.gender = NULL,
method = c("tdt", "hhrr", "trimm"), names.marker = NULL,
use.haplotypes = FALSE, use.ambiguous = TRUE, design = "triad",
markers = "ALL", n.vars = 0, sep = " ", allele.sep = ";",
na.strings = "NA", use.missing = FALSE, xchrom = FALSE,
sex = NULL, threshold = 0.01, verbose = TRUE, printout = TRUE)Of the following arguments, only filename is required. Use of the remaining arguments will depend on the type of analysis.
A character string giving the name and path of the ASCII data file to be read.
Number of permutations. Default is 0, which means that haplinTDT does not do
a permutation test.
Do the analysis for a gender subset. Values: 1, 2, or NULL. 1: Male, 2: Female, NULL: All. Default is NULL.
A character vector containing the methods that are used int the analysis. Possible values are "tdt", "hhrr" and "trimm". Default are all three.
Marker names. Default is NULL which means that the markers are denoted 1, 2, ..., # markers.
A logical value, default is FALSE. If
use.haplotypes=TRUE haplotypes corresponding to the individual
markers are reconstructed by haplin using the EM
algorithm.
The haplotypes are then
analysed as a single multiallelic marker. If use.haplotypes=FALSE,
the markers are analysed individually.
A logical value, default is TRUE. If FALSE then we remove those family triads where it is ambiguous which allele is transferred to the child from a parent.
For the moment only the value "triad" is allowed. It is used for the standard case triad design, without independent controls.
Default is "ALL", which means haplinTDT uses all
available markers in the data set in the analysis. If
use.haplotypes = TRUE then for the current
version of haplin the number of markers used at a single run
should probably not exceed 4 or 5 due to the computational
burden. The markers argument can be used to select appropriate
markers from the file without creating a new file for the selected
markers. For instance, if markers is set to c(2,4), haplinTDT will
only use the second and fourth markers supplied in the data
set. When running haplinTDT, it may be a good idea to start
exploring a few markers at a time, using this argument.
Numeric. The number of variables (columns) in the data file before (to the left) of the genetic data.
The character separator used in the data file to separate between "columns", where each column contains the two alleles of a single individual at a single marker.
The character separator used in the data file to separate the two alleles for a single individual in a single marker. The recommended (default) separator is ";", but for SNPs an empty "" is also common.
The character string indicating missing data in the data file. Default is to use "NA" in place of, for instance, C;T for a SNP that hasn't been typed in that individual.
A logical value used to determine whether triads
with missing data should be included in the analysis. When set to
TRUE, haplinTDT uses haplin to reconstruct the markers or haplotypes. The default, however, is
FALSE. When FALSE, all triads having any sort of missing data are
excluded before the analysis is run. Note that haplinTDT only looks at
markers actually used in the analysis, so that if the markers
argument (see below) is used to select a collection of markers for
analysis, haplinTDT only excludes triads with missing data on the
included markers.
Logical, defaults to "FALSE". If set to "TRUE",
haplinTDT assumes the markers are on the x-chromosome. This option
should be combined with specifying the sex argument.
A numeric value specifying which of the data columns that
contains the sex variable. The variable should be coded 1 for males
and 2 for females. To be used with xchrom = TRUE.
Sets the (approximate) lower limit for the haplotype frequencies of those haplotypes that should be retained in the analysis. Hapotypes that are less frequent are removed, and information about this is given in the output.
Default is T (=TRUE).
Logical. If TRUE (default), haplinTDT prints a full
summary of the results after finishing the estimation. If FALSE, no
such printout is given, but the summary function can later be
applied to a saved result to get the same summary.
An object of class haplinTDT is returned
Threee types of transmission disequilibrium tests (TDT) are provided:
Let t_ij be the number of parents transmitting allele i and not j to its child and let n be number of alleles. The standard TDT test is then defined as the sum of terms (t_ij - t_ji)^2/(t_ij + t_ji) for 1<=i<j<=n. This sum is asymptotically chi-squared with n(n-1) degrees of freedom when the marker and disease loci are unlinked or not associated.
Let t_i. and t_.i be the marginal totals of t_ij. The Haplotype-based haplotype relative risk (HHRR) test is then defined as the sum of (t_i. - t_.i)^2/(t_i. + t_.i) for i = 1, 2, ..., n. The HHRR test statistic is asymptotically chi-squared with n-1 degrees of freedom.
The Triad Multi-Marker test (TRIMM) test is only defined for diallelic markers.
If use.ambiguous = FALSE, then all ambiguous trios will be removed. Otherwise, the different contributions to TDT, HHRR and TRIMM are weighted with the probabilities of the different transmission configurations of alleles from parent to child. For example if the parents and the child are all heterozygous 1/2, then with probability 0.5 the mother (or father) will transfer allele 1 and not allele 2. The standard formulation of the TDT and HHRR tests correspond to having use.ambiguous = TRUE.
Haplotype-based haplotype haplotype relative risk (HHRR): Terwilliger JD and Ott J. A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. Human Heredity (1992) 42(6), pp. 337-46.
Transmission disequilibrium test (TDT): Spielman RS, McGinnis RE and Ewens WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). American Journal of Human Genetics (1993) 52(3), pp. 506-16.
Triad multi-marker test (TRIMM): Shi M, Umbach DM and Weinberg CR. Identification of risk-related haplotypes with the use of multiple SNPs from nuclear families. The American Journal of Human Genetics (2007) 81, pp. 53-66.
# NOT RUN {
# }
# NOT RUN {
# Standard run with permutation test:
res <- haplinTDT("data.dat", nsim.perm=1000)
# Plot the saved result:
plot(res)
# A full summary of saved result including p-values
summary(res)
# Include missing values:
res <- haplinTDT("data.dat", nsim.perm=1000, use.missing=TRUE)
# }
# NOT RUN {
# }
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