Introduction

There is a nice vignette in snpStats concerning linkage disequilibrium (LD) analysis as supported by software in that package. The purpose of this package is to simplify handling of existing population-level data on LD for the purpose of flexibly defining LD blocks.

Import of HapMap LD data

The hmld function imports gzipped tabular data from hapmap’s repository .

suppressPackageStartupMessages({
 library(ldblock)
 library(GenomeInfoDb)
})
path = dir(system.file("hapmap", package="ldblock"), full=TRUE)
ceu17 = hmld(path, poptag="CEU", chrom="chr17")

## importing /tmp/RtmpvnQ8eK/Rinst18c62ea6fba8/ldblock/hapmap/ld_chr17_CEU.txt.gz

## done.

ceu17

## ldstruct for population CEU, chrom chr17
## dimensions: 36621 x 36621 ; statistic is Dprime 
## object structure:
##       ldmat       chrom      genome      allpos      poptag   statInUse 
## "dsCMatrix" "character" "character"   "numeric" "character" "character" 
##       allrs 
## "character"

A view of the block structure

For some reason knitr/render will not display this image nicely.

library(Matrix)

## 
## Attaching package: 'Matrix'

## The following object is masked from 'package:S4Vectors':
## 
##     expand

image(ceu17@ldmat[1:400,1:400], 
   col.reg=heat.colors(120), colorkey=TRUE, useRaster=TRUE)

This ignores physical distance and MAF. The bright stripes are probably due to SNP with low MAF.

Collecting SNPs exhibiting linkage to selected SNP

We’ll use ceu17 and the gwascat package to enumerate SNP that are in LD with GWAS hits.

library(gwascat)

## gwascat loaded.  Use makeCurrentGwascat() to extract current image.

##  from EBI.  The data folder of this package has some legacy extracts.

load(system.file("legacy/ebicat37.rda", package="gwascat"))
#seqlevelsStyle(ebicat37) = "NCBI"  # noop?
seqlevels(ebicat37) = gsub("chr", "", seqlevels(ebicat37))
e17 = ebicat37[ which(as.character(seqnames(ebicat37)) == "17") ]

Some dbSNP names for GWAS hits on chr17 are

rsh17 = unique(e17$SNPS)
head(rsh17)

## [1] "rs11078895" "rs11891"    "rs7501939"  "rs9905704"  "rs4796793" 
## [6] "rs78378222"

We will use expandSnpSet to obtain names for SNP that were found in HapMap CEU to have which D′ > .9 with any of these hits. These names are added to the input set.

length(rsh17)

## [1] 530

exset = ldblock::expandSnpSet( rsh17, ldstruct= ceu17, lb=.9 )

## Warning in ldblock::expandSnpSet(rsh17, ldstruct = ceu17, lb = 0.9): dropping
## 149 rsn not matched in ld matrix

length(exset)

## [1] 13209

all(rsh17 %in% exset)

## [1] TRUE

Not all GWAS SNP are in the HapMap LD resource. You can use your own LD data as long as the format agrees with that of the HapMap distribution.