assocCoxPH {GWASTools} | R Documentation

## 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)

[Package GWASTools version 1.36.0 Index]