RVsharing (version 1.7.0)

RVgene_allshare: Probability of sharing of rare variants among all affected relatives in a family sample within a gene

Description

Computing probability of sharing of rare variants among all affected relatives in a family sample within a genomic region such as a gene.

Usage

RVgene_allshare(ped.mat,ped.listfams,sites,fams,pshare.vec,
type="alleles",minor.allele.vec,precomputed.prob=list(0),maxdim = 1e9)

Arguments

ped.mat

a data.frame or matrix encoding the pedigree information and genotype data in the standard LINKAGE ped format (see PLINK web site [1]). In fact, only the family ID in the first column, the subject ID in the second column, the affection status in the sixth column and the genotype data starting in the seventh column are used (columns 3 to 5 are ignored). Also, family members without genotype data do not need to appear in this matrix. The genotype of each variant can be coded in two ways, each corresponding to a different value of the type option: a minor allele count on one column, as returned for example by the genotypeToSnpMatrix function, with missing values coded NA (type="count") or the identity of the two alleles on two consecutive columns, with missing values coded 0 (type="alleles").

ped.listfams

a list of pedigree objects, one object for each pedigree in ped.mat.

sites

a vector of the column indices of the variant sites to test in ped.mat. If the argument fams is provided, the variant sites are tested in each corresponding family in the fams vector (a variant present in multiple families must then be repeated for every families where it appears).

fams

an optional character vector of the names of families in ped.mat and ped.listfams carrying the variants listed in the corresponding position in sites. If missing, the names of the families carrying the minor allele at each position in sites are extracted from ped.mat.

pshare.vec

a vector of the probabilities that all affected relatives share a rare variant, for every family. This vector must be named with the family names.

type

an optional character string taking value "alleles" or "count". Default is "alleles".

minor.allele.vec

an optional vector of the minor alleles at each site in the sites vector. It is not needed if type="count". If it is missing and type="alleles", the minor allele is assumed to take the value 2.

precomputed.prob

an optional list of vectors precomputed rare variant sharing probabilities for families in ped.mat and ped.listfams. The vectors represent probabilities for all the possible values of N.list for the corresponding family (one probability per value of N.list).

maxdim

upper bound on the dimension of the array containing the joint distribution of the sharing patterns for all families in fams (to avoid running out of memory).

Value

A list with items:

pall

P-value of the exact rare variant sharing test requiring sharing by all affected subjects.

potentialp

Minimum achievable p-value if all affected subjects were carriers of a rare variant.

Details

The function extracts the carriers of the minor allele at each entry in sites in each family where it is present in ped.mat (or in the families specified in fams if that argument is specified). It then computes exact rare variant sharing probabilities in each family for each variant by calling RVsharing. If multiple rare variants are seen in the same family, the smallest sharing probability among all rare variants is retained. The families where all affected subjects share a rare variant are determined by verifying if the length of the carrier vector equals the number of affected subjects that family. The joint rare variant sharing probability over all families is obtained as the product of the family-specific probabilities. The p-value of the test requiring sharing by all affected subjects is computed by calling get.psubset.

References

[1] http://pngu.mgh.harvard.edu/~purcell/plink/data.shtml#ped [2] 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.

See Also

RVsharing,get.psubset

Examples

data(ped.list)
data(ex.ped.mat)
plot(ped.list[[49]])
plot(ped.list[[13]])

ex.ped.obj = ped.list[c(13,49)]
names(ex.ped.obj) = c("15157","28003")
# Computation of RV sharing probability by all affected relatives in families 28003 and 15157
pshare.vec = c(RVsharing(ped.list[[13]],)@pshare,RVsharing(ped.list[[49]])@pshare)
names(pshare.vec) = c("15157","28003")

sites = c(92,119)
minor.allele.vec=c(1,4)

RVgene_allshare(ex.ped.mat,ex.ped.obj,sites,pshare.vec=pshare.vec,minor.allele.vec=minor.allele.vec)