assocCoxPH: Cox proportional hazards

In smgogarten/GWASTools: Tools for Genome Wide Association Studies

Cox proportional hazards

Description

Fits Cox proportional hazards model

Usage

assocCoxPH(genoData,
           event,
           time.to.event,
           gene.action = c("additive", "dominant", "recessive"),
           covar = NULL,
           ivar = NULL,
           strata = NULL,
           cluster = NULL,
           scan.exclude = NULL,
           LRtest = FALSE,
           effectAllele = c("minor", "alleleA"),
           snpStart = NULL,
           snpEnd = NULL,
           block.size = 5000,
           verbose = TRUE)

Arguments

genoData	a GenotypeData object
event	name of scan annotation variable in genoData for event to analyze (chould be coded 0/1 or FALSE/TRUE)
time.to.event	name of scan annotation variable in genoData for time to event
gene.action	"additive" coding sets the marker variable for homozygous minor allele samples = 2, heterozygous samples = 1, and homozygous major allele samples = 0. "dominant" coding sets the marker variable for homozygous minor allele samples = 2, heterozygous samples = 2, and homozygous major allele samples = 0. "recessive" coding sets the marker variable for homozygous minor allele samples = 2, heterozygous samples = 0, and homozygous major allele samples = 0. (If effectAllele="alleleA", the coding reflects alleleA instead of the minor allele.)
covar	a vector of the names of the covariates to adjust for (columns in the scan annotation of genoData)
ivar	the name of the variable in covar to include as an interaction with genotype
strata	a vector of names of variables to stratify on for a stratified analysis
cluster	the name of a column (in the scan annotation of genoData) which clusters the observations for robust variance. See cluster

.

scan.exclude	a vector of scanIDs for scans to exclude
LRtest	logical for whether to perform Likelihood Ratio Tests in addition to Wald tests (which are always performed).
effectAllele	whether the effects should be returned in terms of the minor allele for the tested sample (effectAllele="minor") or the allele returned by getAlleleA(genoData) (effectAllele="alleleA"). If the minor allele is alleleB for a given SNP, the difference between these two options will be a sign change for the beta estimate.
snpStart	index of the first SNP to analyze, defaults to first SNP
snpEnd	index of the last SNP to analyze, defaults to last SNP
block.size	number of SNPs to read in at once
verbose	logical for whether to print status updates

Details

This function performs Cox proportional hazards regression of a survival object (using the Surv function) on SNP genotype and other covariates. It uses the coxph function from the R survival library.

It is recommended to filter results returned using 2*MAF*(1-MAF)*n.events > 75 where MAF = minor allele frequency and n.events = number of events. This filter was suggested by Ken Rice and Thomas Lumley, who found that without this requirement, at threshold levels of significance for genome-wide studies, Cox regression p-values based on standard asymptotic approximations can be notably anti-conservative.

Note: Y chromosome SNPs must be analyzed separately because they only use males.

Value

a data.frame with some or all of the following columns:

snpID	the snpIDs
chr	chromosome SNPs are on
n	number of samples used to analyze each SNP
n.events	number of events in complete cases for each SNP
effect.allele	which allele ("A" or "B") is the effect allele
EAF	effect allele frequency
MAF	minor allele frequency
maf.filter	TRUE if SNP passes the MAF filter (2*MAF*(1-MAF)*n.events > 75)
Est	beta estimate for genotype
SE	standard error of beta estimate for the genotype
Wald.Stat	chi-squared test statistic for association
Wald.pval	p-value for association
LR.Stat	likelihood ratio test statistic for association
LR.pval	p-value for association
GxE.Est	beta estimate for the genotype*ivar interaction parameter (NA if this parameter is a factor with >2 levels)
GxE.SE	standard error of beta estimate for the genotype*ivar interaction parameter
GxE.Stat	Likelihood ratio test statistic for the genotype*ivar interaction parameter
GxE.pval	p-value for the likelihood ratio test statistic

Author(s)

Cathy Laurie, Matthew Conomos, Stephanie Gogarten, David Levine

See Also

GenotypeData, coxph

Examples

library(GWASdata)
data(illuminaScanADF)
scanAnnot <- illuminaScanADF

# exclude duplicated subjects
scan.exclude <- scanAnnot$scanID[scanAnnot$duplicated]

# create some variables for the scans
scanAnnot$sex <- as.factor(scanAnnot$sex)
scanAnnot$age <- rnorm(nrow(scanAnnot), mean=40, sd=10)
scanAnnot$event <- rbinom(nrow(scanAnnot), 1, 0.4)
scanAnnot$ttoe <- rnorm(nrow(scanAnnot), mean=100, sd=10)

# create data object
gdsfile <- system.file("extdata", "illumina_geno.gds", package="GWASdata")
gds <- GdsGenotypeReader(gdsfile)
genoData <-  GenotypeData(gds, scanAnnot=scanAnnot)

res <- assocCoxPH(genoData,
                  event="event", time.to.event="ttoe",
  		  covar=c("sex", "age"),
  		  scan.exclude=scan.exclude,
  		  snpStart=1, snpEnd=100)

close(genoData)

smgogarten/GWASTools documentation built on Nov. 10, 2024, 9:54 p.m.