RVsharing-methods: probability of sharing a rare variant among relatives

In RVS: Computes estimates of the probability of related individuals sharing a rare variant

Description

computing probability that a rare variant is shared by a set of subjects in a pedigree using the gRain package

Usage

RVsharing(
  ped,
  carriers = NULL,
  alleleFreq = NA,
  kinshipCoeff = NA,
  nSim = NA,
  founderDist = NULL,
  useAffected = FALSE,
  kinshipOrder = 5,
  splitPed = FALSE,
  useFounderCouples = TRUE,
  ...
)

## S4 method for signature 'pedigree'
RVsharing(
  ped,
  carriers = NULL,
  alleleFreq = NA,
  kinshipCoeff = NA,
  nSim = NA,
  founderDist = NULL,
  useAffected = FALSE,
  kinshipOrder = 5,
  splitPed = FALSE,
  useFounderCouples = TRUE,
  ...
)

## S4 method for signature 'list'
RVsharing(
  ped,
  carriers = NULL,
  alleleFreq = NA,
  kinshipCoeff = NA,
  nSim = NA,
  founderDist = NULL,
  useAffected = FALSE,
  kinshipOrder = 5,
  splitPed = FALSE,
  useFounderCouples = TRUE,
  ...
)

Arguments

ped	S3 pedigree object or a list of pedigree objects
carriers	subjects in pedigree that have the variant, if ped is a list, then this will also be a list of vectors specifying the carriers in each pedigree
alleleFreq	allele frequency among the founders
kinshipCoeff	mean kinship coefficient among the founders
nSim	number of simulations used in monte carlo calculation
founderDist	custom distribution among founders. Only used when simulating probability with nSim
useAffected	a logical value indicating whether to condition on seeing the variant among the affected subjects instead of the final descendants
kinshipOrder	order of the polynomial approximation to the distribtion of the number of distinct alleles in the founders (d in Bureau et al.). Must be <= 5
splitPed	a logical value indicating whether to split the pedigree in subpedigrees below each founder to enable computations in pedigrees too large to be stored in a single Bayesian network
useFounderCouples	a logical value indicating whether to exploit the interchangeability of the mother and father from founder couples to save computations. Warning! This works only when all founders have only one spouse. Set to FALSE if at least one founder has two or more spouses. Only used when splitPed = TRUE
...	allows for additional arguments

Details

the function RVsharing computes the probability that all subjects identified as carriers of a rare variant in the vector carriers (or all final descendants in the pedigree if carriers == NULL) share that rare variant AND the final descendants not included in carriers do not carry it, given that the rare variant has been detected in any subject in the union of the carriers and the final descendants of the pedigree. A final descendant is defined as a subject without descendant in the pedigree, it it not necessarily in the youngest generation. If carriers enumerates a subset of pedigree members, the function will then compute the probability these carriers share the rare variant AND the final descendants not included in carriers do not carry it based on the above terms. To obtain the probability that a set of pedigree members carry a rare variant given it was seen in any of the set members (ignoring the carrier status of final descendants not in the set), the pedigree must be trimmed of the other final descendants before calling RVsharing.

Value

sharing probability between all carriers in pedigree, or if splitPed = TRUE, a vector of sharing probabilities for all subsets of the carriers

References

Bureau, A., Younkin, S., Parker, M.M., Bailey-Wilson, J.E., Marazita, M.L., Murray, J.C., Mangold, E., Albacha-Hejazi, H., Beaty, T.H. and Ruczinski, I. (2014) Inferring rare disease risk variants based on exact probabilities of sharing by multiple affected relatives. Bioinformatics, 30(15): 2189-96, doi:10.1093/bioinformatics/btu198.

Sherman, T., Fu, J., Scharpf, R., Bureau, A., and Ruczinski, I. (2018) Detection of rare disease variants in extended pedigrees using RVS. Bioinformatics, 1-3, doi: 10.1093/bioinformatics/bty976

Examples

data("samplePedigrees")
RVsharing(samplePedigrees$firstCousinPair)

RVS documentation built on Nov. 8, 2020, 6:57 p.m.