FAIncidenceRateResults: Familial Incidence Rate

In EuracBiomedicalResearch/FamAgg: Pedigree Analysis and Familial Aggregation

Familial Incidence Rate

Description

The FAIncidenceRateResults object contains the results from a familial incidence rate calculation employing in addition Monte Carlo simulations to assess significance levels for the familial incidence rate of each individual. The familial incidence rate (FIR, also referred to as FR in Kerber (1995)) is an estimate for the risk per gene-time for each individuals for a certain disease given the disease experience in the cohort. The measure considers the kinship of each individual with any affected individual in the pedigree and the time at risk for each.

Note that in contrast to e.g. FAKinSumResults a familial incidence rate and corresponding p-value are calculated and available for all individuals in the pedigree, not only for affected individuals.

Usage

## S4 method for signature 'FAIncidenceRateResults'
familialIncidenceRate(object, trait=NULL,
                                                         timeAtRisk=NULL,
                                                         ...)

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

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

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

## S4 method for signature 'FAIncidenceRateResults'
runSimulation(object, nsim=50000,
                                                 timeAtRisk=NULL,
                                                 strata=NULL, ...)

## S4 method for signature 'FAIncidenceRateResults'
timeAtRisk(object)

## S4 replacement method for signature 'FAIncidenceRateResults'
timeAtRisk(object) <- value

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

Arguments

(in alphabetic order)

addLegend	For plotRes: if a legend should be added to the plot.
device	For plotPed: see plotPed for more details.
family	For plotPed: the family for which the pedigree should be plotted. For plotRes: not supported.
filename	For plotPed: the file name to which the pedigree plot should be exported. See plotPed for more details.
id	For plotPed and plotRes: the id of the indiviual for which the pedigree or the simulation result should be plotted. Note: id can be a numeric or a character. Numeric ids will be internally converted to character.
method	The multiple hypothesis testing method. All methods supported by p.adjust are allowed.
nsim	Number of simulations.
object	The FAIncidenceRateResults object.
only.phenotyped	For plotPed: Wheter only phenotyped individuals, i.e. individuals with a non-NA value in column affected (the trait information). If TRUE, the function removes all non-phenotyped individuals, keeping only those that are required for the pedigree to be complete.

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 on the PedigreeAnalysis help page or examples for more information.
timeAtRisk	For runSimulation: a numeric vector specifying the time at risk for each individual in the given trait. See also estimateTimeAtRisk, an utility function to estimate time at risk. For familialIncidenceRate: not used.
trait	For familialIncidenceRate: not used.
type	For plotRes: at present only "density" is supported.
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 timeAtRisk: a numeric vector with the time at risk for each individual.
...	For plotPed: additional arguments to be submitted to the internal buildPed call and to plotPed. For runSimulation: additional arguments prune and lowMem. See below for details.

Details

Monte Carlo simulation and empirical p-value estimation: the background distribution to calculate the p-value for a familial incidence rate (FIR) is determined by randomly sampling N affected individuals (N being the number of affected) and calculating the expected FIR for all individuals in each simulation iteration. The p-value for an individual represents thus the number of times an expected FIR for that individual from the simulation was found to be larger than or equal to the observed FIR divided by the number of iterations.

Calling the runSimulation method on a FAIncidenceRateResults object is the same as calling the familialIncidenceRateTest on a FAData object. In the first case the simulation is performed using the trait information data stored internally in the object, while in the latter case the trait information have to be submitted to the function call.

By providing argument strata, the stratified random sampling is performed. See example below and the details section in PedigreeAnalysis for more details.

The familial incidence rate can also be directly calculated, without simulation, using the familialIncidenceRate method of a FAData object.

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.

By default the Monte Carlo p-value estimation in the runSimulation method is quite memory demanding. For very large pedigrees the optional argument lowMem=TRUE might be passed to the method which results in faster and less memory demanding calculations. This will however disable the plotRes method on the resulting FAIncidenceRateResults as the distribution of familial incidence rates from the simulation runs is no longer reported.

Note: the FIR for singletons and individuals that do not share kinship with at least one other phenotyped individual that has also a valid value in argument timeAtRisk (and eventually strata) will be NA.

Value

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

Objects from the Class

FAIncidenceRateResults objects are created by the familialIncidenceRateTest method on a FAData object.

Extends

Class FAData directly.

Slots

nsim

Number of simulations.

sim

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

timeAtRisk

Numeric vector with the time at risk for each individual. Use the accessor method timeAtRisk or use object$tar to extract this data.

Methods and Functions

object$name

Access the familial incidence rate using object$fir, the (raw) p-value from the simulation using object$pvalue and the time at risk for each individual using object$tar or object$timeAtRisk with object being the FAIncidenceRateResults object.

familialIncidenceRate

Returns the familial incidence rate values calculated by a call to the runSimulation method or familialIncidenceRate method on a FAData object. In contrast to that latter method, which directly calculates the values, this method returns the values from a calculation stored inside the FAIncidenceRateResults object.

The method returns a named numeric vector with the familial incidence rates for all individuals in the pedigree, the names being the ID of the individuals. Singletons as well as individuals that, after removing not phenotyped individuals or individuals without time at risk, do not share kinship with any other individual in the pedigree have a value of NA.

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. The familial incidence rate value for each individual is drawn below the individual's id. See plotPed for more details.

plotRes

Plots the distribution of expected familial incidence rates calculated for the selected individuals from Monte Carlo simulations along with the actually observed familial incidence rate.

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 phenotyped individuals in the trait.

"total_affected": total number of affected individuals in the trait.

"total_tested": the number of individuals in the pedigree considered for the simulation. This corresponds to all individuals with valid, non-NA, values in trait, timeAtRisk and eventually strata.

"id": the id of the individual.

"family": the family id.

"fir": the familial incidence rate. Note that this will be

NA for all non-phenotyped individuals and singletons in the pedigree as well as for individuals that do not share kinship with at least one other phenotyped individual with valid time at risk (or valid value in parameter strata).

"pvalue": the p-value for the significance of the familial incidence rate assessed by Monte Carlo simulations.

"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 row names correspond to column "id".

runSimulation

Performs the simulation analysis based on the pedigree and trait information stored in the object as well as the time at risk provided with argument timeAtRisk. Returns a FAIncidenceRateResults object with the results from 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

Kerber, R.A. (1995) Method for calculating risk associated with family history of a disease. Genet Epidemiol, pp 291–301.

See Also

FAData, kinship, trait, probabilityTest, kinshipGroupTest, kinshipSumTest, genealogicalIndexTest, familialIncidenceRateTest, fsirTest, plotPed, estimateTimeAtRisk

Examples

##########################
##
##  Perform the simulation analysis
##
## Load the test data.
data(minnbreast)

## Subset to some families and generate a pedigree data.frame.
mbsub <- minnbreast[minnbreast$famid == 4 | minnbreast$famid == 5 |
                    minnbreast$famid == 6 | minnbreast$famid == 7 |
                    minnbreast$famid == 411, ]
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

## Spefify the "time at risk"; we are using column "endage"
tar <- mbsub$endage

## Perform the simulation test:
far <- familialIncidenceRateTest(fad, trait=tcancer, traitName="cancer",
                                 timeAtRisk=tar, nsim=1000)
head(result(far))

## We can easily extract the actual FIR values:
head(far$fir)
## Or
head(familialIncidenceRate(far))

## Access the p-value directly.
head(far$pvalue)

## Access the time at risk
head(timeAtRisk(far))
head(far$tar)
head(far$timeAtRisk)

## Plot the pedigree for a family with significant FIRs.
## The numbers below the IDs of the individuals represent the actual
## FIR values.
plotPed(far, family=result(far)$family[1])

## Plot also the result from the simulation run.
plotRes(far, id=result(far)$id[1])

EuracBiomedicalResearch/FamAgg documentation built on March 12, 2023, 7:45 p.m.