FAGenIndexResults-class {FamAgg} | R Documentation

## Genealogical Index

### Description

The genealogical index [Hill, 1980], also referred to as the genealogical index of familiality (GIF) in the literature, is a method to identify familial clustering of diseases or other traits. For a given trait, the method computes the mean kinship between affected in the whole pedigree along with mean kinships of randomly drawn sets of individuals. The distribution of average kinship values among the control sets is used to estimate the probability that the observed level of kinship among the cases is due to chance.

### Usage

    ## S4 method for signature 'FAGenIndexResults'
    plotPed(object, id=NULL, family=NULL,
                                         filename=NULL, device="plot", ...)

    ## S4 method for signature 'FAGenIndexResults'
    plotRes(object, id=NULL, family=NULL,
                                         addLegend=TRUE, type="density", ...)

    ## S4 method for signature 'FAGenIndexResults'
    result(object, method="BH")

    ## S4 method for signature 'FAGenIndexResults'
    runSimulation(object, nsim=50000,
                                               perFamilyTest=FALSE,
                                               controlSetMethod="getAll",
                                               rm.singletons=TRUE, strata=NULL, ...)

    ## S4 replacement method for signature 'FAGenIndexResults'
    trait(object) <- value

### Arguments

(in alphabetic order)

`addLegend` | For `plotRes`: if a legend should be added to the plot.
`controlSetMethod` | For `runSimulation`: the method (i.e. name of the function) that should be used to define the set of (eventually matched) control individuals from which the random samples are taken. Supported functions are `getAll`, `getSexMatched` and `getExternalMatched`. For `perFamilyTest=TRUE` also `getGenerationMatched` and `getGenerationSexMatched` are supported. Note: for `getExternalMatched`, a numeric, character or factor vector to be used for the matching has to be submitted to `runSimulation` as additional argument `match.using`.
`device` | For `plotPed`: see `plotPed` for more details.
`family` | For `plotPed`: the family for which the pedigree should be plotted. For `plotRes`: the family for which the genealogical index analysis simulation results should be shown. Only supported if `perFamilyTest=TRUE`.
`filename` | For `plotPed`: the file name to which the pedigree plot should be exported. See `plotPed` for more details.
`id` | For `plotPed`: the id of an indiviual from a family for which the pedigree should be plotted. For `plotRes`: the id of an individual from a family for which the genealogical index analysis simulation results should be shown. Only supported if `perFamilyTest=TRUE`.
`method` | The multiple hypothesis testing method. All methods supported by `p.adjust` are allowed.
`nsim` | Number of simulations.
`perFamilyTest` | For `runSimulation`: whether the test should be performed on the whole pedigree (default) or separately within each family. In the latter case the test evaluates the presence of clustered affected individuals within each family.
`rm.singletons` | For `runSimulation`: whether unconnected individuals in the pedigree (i.e. singletons) should be removed.
`object` | The `FAGenIndexResults` object.
`strata` | For `runSimulation`: a numeric, character of factor characterizing each individual in the pedigree. The length of this vector and the ordering has to match the pedigree. This vector allows to perform stratified random sampling. See details or examples for more information.
`type` | For `plotRes`: either `"density"` (the default) or `"hist"` specifying whether the distribution of expected values from the simulation should be visualized as a density plot or histogram.
`value` | For `trait<-`: can be a named numeric, character or factor vector. The names (at least some of them) have to match the ids in the pedigree of the object.
`...` | For `plotPed`: additional arguments to be submitted to the internal `buildPed` call and to `plotPed`. For `runSimulation`: additional arguments passed to the choosen `controlSetMethod` function (e.g. `match.using` for `getExternalMatched`).

### Details

This implementation differs from the original method from Hill as it allows, in addition to perform per family analyses, to use also stratified sampling and allows a more flexible definition of the set of matched control individuals. The `controlSetMethod` parameter allows to specify a method to define the matched control set (e.g. matched by sex or matched by any externally provided vector).

Stratified sampling allows to even further fine tune the selection of matched controls. Assuming that in a pedigree the group of affected consists of 5 females and 3 male individuals, passing the sex of all individuals to the function (e.g. `strata=fad$sex`, with `fad` being the `FAData` object containing the pedigree to be analyzed) results in random sets with the same proportion of male/female individuals (i.e. 5 females, 3 males).

Note that, if `strata` is specified, all individuals with a missing value in `strata` (also affected individuals) are excluded from the analysis.

Note that by default singletons (i.e. unconnected individuals in the pedigree) are removed from the pedigree prior the analysis. Set `rm.singletons=FALSE` if you do not want them to be removed.

By default, the genealogical index is calculated on the whole pedigree, but it is also possible to evaluate within-family clustering of cases by specifying `perFamilyTest=TRUE`. In that case, it is also possible to use the `getGenerationMatched` and `getGenerationSexMatched` functions to define the set of matched controls from which random samples will be taken.

A call to the setter methods `trait<-` resets any simulation results present in the `sim` slot, thus, the object can be re-used to perform a simulation analysis using the new trait data.

### Value

Refer to the method and function description above for detailed information on the returned result object.

### Objects from the Class

`FAGenIndexResults` objects are created calling the `genealogicalIndexTest` method on a `FAData` object.

### Extends

Class `FAData` directly.

### Slots

controlSetMethod

  A character specifying the name of the method used to define the set of control individuals from which random samples were taken.

nsim

  Number of simulations.

perFamilyTest

  Logical indicating whether a per-family test was performed.

sim

  The result of the simulation. This slot should not be accessed directly, use the `result` method to extract result information.

### Methods and Functions

`plotPed` Plots a pedigree for one of the affected individuals in the simulation results. The id of the selected affected individual (specified with argument `id`) is highlighted in red. See `plotPed` for more details.

`plotRes` Plots the results from a genealogical index simulation analysis. The distribution of the mean kinship values of the randomly drawn controls are displayed as a grey density plot, the observed mean kinship value of all affected as a blue vertical line.

result

  Returns the result from the simulation as a `data.frame` with columns: `"trait_name"`: the name of the trait. `"total_phenotyped"`: total number of individuals in the pedigree phenotyped in the analyzed trait. `"total_affected"`: total number ofindividuals in the pedigree that are affected in the analyzed trait (i.e. number of cases). `"entity_id"`: the id for the analyzed entity, being either the whole pedigree (in which case the id will be `"1"`) or the id of the family (if `perFamilyTest=TRUE`). `"entity_ctrls"`: the number of (matched) control individuals from which the random samples were drawn. `"entity_affected"`: the number of affected individuals in the entity. This number can differ from the number of affected, if `strata` was specified and some of the affected have a missing value in `strata`. `"genealogical_index"`: the genealogical index of familiality (gif), i.e. the mean kinship value between all affected in the entity (pedigree or family). To be consistent with the original implementations, the genealogical index is the mean kinship multiplied with 100000. `"pvalue"`: the p-value for the significance of the mean kinship. `"padj"`: the p-value adjusted for multiple hypothesis testing (with the method specified with argument `method`).

  The returned `data.frame` is sorted by column `"pvalue"`, its rownames correspond to column `"entity_id"`.

runSimulation

  Performs the simulation analysis based on the pedigree and trait information stored in the object. Returns a `FAGenIndexResults` object with the results of the simulation.

trait<-

  Set the trait information. This method will reset all simulation results saved in the `sim` slot.

### Note

Subsetting (using the `[` operator) is not supported.

### Author(s)

Johannes Rainer

### References

Hill, J. R. (1980) A survey of cancer sites by kinship in the Utah Mormon population. In Cairns J, Lyon JL, Skolnick M (eds): Cancer Incidence in Defined Populations. Banbury Report 4. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, pp 299–318.

### See Also

`FAData`, `trait`, `probabilityTest`, `kinshipGroupTest`, `kinshipSumTest`, `familialIncidenceRateTest`, `fsirTest`, `plotPed`

### Examples

    ##########################
    ##
    ##  Perform the simulation analysis
    ##
    ## Load the Minnesota Breast Cancer data set.
    data(minnbreast)

    ## Subset to some families and generate a pedigree data.frame
    mbsub <- minnbreast[minnbreast$famid == 4 | minnbreast$famid == 14 |
                      minnbreast$famid == 6 | minnbreast$famid == 8, ]
    PedDf <- mbsub[, c("famid", "id", "fatherid", "motherid", "sex")]
    colnames(PedDf) <- c("family", "id", "father", "mother", "sex")

    ## Generate the FAData.
    fad <- FAData(pedigree=PedDf)

    ## Specify the trait.
    tcancer <- mbsub$cancer
    names(tcancer) <- mbsub$id

    ## Perform the test with default settings, i.e. use all individuals
    ## in the pedigree as control set from which random samples are drawn
    ## and perform the analysis on the whole pedigree.
    gi <- genealogicalIndexTest(fad, trait=tcancer, traitName="cancer",
                                nsim=1000,)
    ## Just show some information
    gi

    ## Show the results
    result(gi)

    ## Plot the observed mean kinship and the distribution of the mean kinship of
    ## random samples.
    plotRes(gi)

    ## Plot the pedigree for one of the families. All individuals
    ## used as matched control set are highlighted in red.
    plotPed(gi, family="8")

    ## Repeat the analysis using the sex as strata. This will result in stratified
    ## random sampling with the number of female and male individuals selected in
    ## each permutation corresponding to the numbers below
    table(gi$sex[affectedIndividuals(gi)])
    giStrata <- runSimulation(gi, nsim=1000, strata=gi$sex)
    result(giStrata)

    ## Alternatively, we can use "getSexMatched" as the function to define the set
    ## of control individuals. Just, in the present case both male and females
    ## individuals will be selected since also there are male and female individuals
    ## among the affected cases.
    giPerFam <- runSimulation(gi, nsim=1000, controlSetMethod="getSexMatched",
                              perFamilyTest=TRUE)
    result(giPerFam)

    ## For those families in which there are only female cases, random samples
    ## were drawn among only female individuals (within the same family). These
    ## are highlighted in red in the pedigree plot:
    plotPed(giPerFam, family="14", cex=0.5)

    ## Plot the simulation result for this family:
    plotRes(giPerFam, family="14")

[Package FamAgg version 1.8.0 Index]