GxE.fitness.score: A function to assign an E-GADGETS (GxGxE) fitness score to a...

In mnodzenski/epistasisGA: An R package to identify multi-snp effects in nuclear family studies using the GADGETS method

A function to assign an E-GADGETS (GxGxE) fitness score to a chromosome

Description

This function assigns the (currently experimental) E-GADGETS fitness score to a chromosome.

Usage

GxE.fitness.score(
  case.genetic.data,
  mother.genetic.data,
  father.genetic.data,
  exposure.mat,
  target.snps,
  weight.lookup,
  null.mean.vec = c(0, 0),
  null.sd.vec = c(1, 1),
  n.different.snps.weight = 2,
  n.both.one.weight = 1
)

Arguments

case.genetic.data	The genetic data of the disease affected children from case-parent trios or disease-discordant sibling pairs. If searching for maternal SNPs that are related to risk of disease in the child, some of the columns in case.genetic.data may contain maternal SNP genotypes (See argument mother.snps for how to indicate which SNPs columns correspond to maternal genotypes). Columns are SNP allele counts, and rows are individuals. This object may either be of class matrix' OR of class 'big.matrix'. If of class 'big.matrix' it must be file backed as type 'integer' (see the bigmemory package for more information). The ordering of the columns must be consistent with the LD structure specified in ld.block.vec. The genotypes cannot be dosages imputed with uncertainty.
mother.genetic.data	The genetic data for the mothers of the cases in case.genetic.data. This should only be specified when searching for epistasis or GxGxE effects based only on case-parent triads, and not when searching for maternal SNPs that are related to the child's risk of disease. Columns are SNP allele counts, rows are individuals. This object may either be of class 'matrix' OR of class 'big.matrix'. If of class big.matrix' it must be file backed as type 'integer' (see the bigmemory package for more information). The genotypes cannot be dosages imputed with uncertainty.
father.genetic.data	The genetic data for the fathers of the cases in case.genetic.data. This should only be specified when searching for epistasis or GxGxE effects based only on case-parent triads, and not when searching for maternal SNPs that are related to the child's risk of disease. Columns are SNP allele counts, rows are individuals. This object may either be of class 'matrix' OR of class 'big.matrix'. If of class big.matrix' it must be file backed as type 'integer' (see the bigmemory package for more information). The genotypes cannot be dosages imputed with uncertainty.
exposure.mat	A matrix of the input categorical and continuous exposures to be used in the experimental E-GADGETS fitness score. If there are categorical exposure variables with more than 2 levels, those should be dummy coded.
target.snps	An integer vector of the columns corresponding to the collection of SNPs, or chromosome, for which the fitness score will be computed.
weight.lookup	A vector that maps a family weight to the weighted sum of the number of different SNPs and SNPs both equal to one.
null.mean.vec	A vector of estimated null means for each of the components of the E-GADGETS fitness score. It should be set to the values of the "null.mean" element of the file "null.mean.sd.info.rds" for the observed data, that is saved by the run.gadgets function.
null.sd.vec	A vector of estimated null means for each of the components of the E-GADGETS fitness score. It should be set to the values of the "null.se" element of the file "null.mean.sd.info.rds" for the observed data, that is saved by the run.gadgets function.
n.different.snps.weight	The number by which the number of different SNPs between a case and complement/unaffected sibling is multiplied in computing the family weights. Defaults to 2.
n.both.one.weight	The number by which the number of SNPs equal to 1 in both the case and complement/unaffected sibling is multiplied in computing the family weights. Defaults to 1.

Value

A list:

fitness.score

The chromosome fitness score.

sum.dif.vecs

The element of the Hotelling-Lawley trace matrix corresponding to each SNP. Larger magnitudes indicate larger contributions to the score, but are otherwise difficult to interpret.

ht_trace

The Hotelling-Lawley trace statistic from the transmission-based fitness score component.

wald_stat

The Wald statistic from the family-based component of the fitness score.

Examples

data(case.gxe)
data(dad.gxe)
data(mom.gxe)
data(exposure)
case.gxe <- case.gxe + 0.0
mom.gxe <- mom.gxe + 0.0
dad.gxe <- dad.gxe + 0.0
exposure <- as.matrix(exposure + 0.0)
weight.lookup <- vapply(seq_len(6), function(x) 2^x, 1.0)
res <- GxE.fitness.score(case.gxe, mom.gxe, dad.gxe, exposure, c(1, 4, 7),
                          weight.lookup)

mnodzenski/epistasisGA documentation built on July 17, 2025, 5:15 a.m.