singlesnpMeta: Meta analyze single snp effects from multiple studies

In seqMeta: Meta-Analysis of Region-Based Tests of Rare DNA Variants

Description

Takes as input 'seqMeta' objects (from the prepScores function), and meta analyzes them.

Usage

singlesnpMeta(..., SNPInfo = NULL, snpNames = "Name",
  aggregateBy = "gene", studyBetas = TRUE, verbose = FALSE)

Arguments

...	seqMeta objects
SNPInfo	The SNP Info file. This should contain the fields listed in snpNames and aggregateBy. Only SNPs in this table will be meta analyzed, so this may be used to restrict the analysis.
snpNames	The field of SNPInfo where the SNP identifiers are found. Default is 'Name'
aggregateBy	The field of SNPInfo on which the skat results were aggregated. Default is 'gene'. Though gene groupings are not explicitely required for single snp analysis, it is required to find where single snp information is stored in the seqMeta objects.
studyBetas	Whether or not to include study-level effects in the output.
verbose	logical. Whether progress bars should be printed.

Details

This function meta analyzes score tests for single variant effects. Though the test is formally a score test, coefficients and standard errors are also returned, which can be interpreted as a 'one-step' approximation to the maximum likelihood estimates.

Value

a data frame with the gene, snp name, meta analysis.

Author(s)

Arie Voorman, Jennifer Brody

References

Lin, DY and Zeng, D. On the relative efficiency of using summary statistics versus individual-level data in meta-analysis. Biometrika. 2010.

See Also

prepScores burdenMeta skatMeta skatOMeta

Examples

###load example data for two studies:
### see ?seqMetaExample
data(seqMetaExample)

####run on each study:
cohort1 <- prepScores(Z=Z1, y~sex+bmi, SNPInfo = SNPInfo, data =pheno1)
cohort2 <- prepScores(Z=Z2, y~sex+bmi, SNPInfo = SNPInfo, data =pheno2)

#### combine results:
out <- singlesnpMeta(cohort1, cohort2, SNPInfo = SNPInfo)
head(out)

## Not run: 
##compare
bigZ <- matrix(NA,2*n,nrow(SNPInfo))
colnames(bigZ) <- SNPInfo$Name
for(gene in unique(SNPInfo$gene)) {
   snp.names <- SNPInfo$Name[SNPInfo$gene == gene]
     bigZ[1:n,SNPInfo$gene == gene][, snp.names \%in\% colnames(Z1)] <- 
             Z1[, na.omit(match(snp.names,colnames(Z1)))]
     bigZ[(n+1):(2*n),SNPInfo$gene == gene][, snp.names \%in\% colnames(Z2)] <- 
             Z2[, na.omit(match(snp.names,colnames(Z2)))]
}

pheno <- rbind(pheno1[ ,c("y","sex","bmi")], pheno2[ , c("y","sex","bmi")])
out3 <- apply(bigZ, 2, function(z) {
         if(any(!is.na(z))) {
           z[is.na(z)] <- mean(z,na.rm=TRUE)
           mod <- lm(y ~ sex+bmi+c(rep(1,n),rep(0,n))+z, data=pheno)
           beta <- mod$coef["z"]
           se <- sqrt(vcov(mod)["z", "z"])
           p <- pchisq( (beta/se)^2,df=1,lower=F)
           return(c(beta,se,p))
         } else {
           return(c(0,Inf,1))
         }
 }) 
 out3 <- t(out3[,match(out$Name,colnames(out3))])
 
 ##plot
 par(mfrow=c(2,2))
 plot(x=out3[,1],y=out$beta, xlab="complete data (Wald)", 
      ylab="meta-analysis (Score)", main="coefficients"); abline(0,1)
 plot(x=out3[,2],y=out$se, xlab="complete data (Wald)", 
      ylab="meta-analysis (Score)", main="standard errors"); abline(0,1)
 plot(x=out3[,3],y=out$p, xlab="complete data (Wald)", 
      ylab="meta-analysis (Score)", main="p-values"); abline(0,1)
 
## End(Not run)

seqMeta documentation built on May 2, 2019, 10:59 a.m.