GWAS track

TL;DR: a GWASTrack renders association results as a Manhattan plot. The main work is prep: a bgzipped, tabix-indexed BED-like file whose score column is in -log₁₀(p) units (or set scoreTransform to convert). Add a PLINK .ld file and colorBy: "ld" to color points by linkage disequilibrium to an index SNP.

Preparing the GWAS file

GWASAdapter reads a bgzipped, tabix-indexed BED-like file with a #-prefixed header row whose score column is in -log₁₀(p) units.

For a file storing raw p-values, set the adapter's scoreTransform slot to negLog10 (raw p-value) or negLog10FromLn (natural-log p-value, e.g. a Pan-UKBB ln P column) and the conversion happens at read time.

Prefix the header so tabix skips it, sort the data rows by chromosome and position, and bgzip/tabix:

# `jbrowse sort-bed` is `sort -k1,1 -k2,2n` with every #-prefixed line kept on
# top rather than sorted into the data, and pins LC_ALL=C so the grouping tabix
# indexes on comes out the same everywhere
sed '1s/^/#/' results.tsv | jbrowse sort-bed | bgzip > results.sorted.txt.gz
tabix -p bed results.sorted.txt.gz

The name column (4th BED field) is the SNP identifier used for LD lookups. If it is absent, lookups fall back to chr:bp (1-based).

Example file:

#chrom  chromStart  chromEnd  name      neg_log_pvalue
chr1    109817590   109817591 rs4970383 1.234
chr1    110162459   110162460 rs4971059 7.891

Preparing the LD file

LD data must be in PLINK --r2 output format. Generate it from a PLINK binary fileset (.bed/.bim/.fam) or a VCF:

# From a PLINK binary fileset. "dprime" adds the D' column (DP)
plink --bfile study --r2 dprime with-freqs \
  --ld-window 99999 --ld-window-kb 1000 --ld-window-r2 0 \
  --out study

# Or starting from a VCF
plink --vcf study.vcf.gz --r2 dprime with-freqs \
  --ld-window 99999 --ld-window-kb 1000 --ld-window-r2 0 \
  --out study

This writes study.ld with columns CHR_A BP_A SNP_A CHR_B BP_B SNP_B R2 (plus DP for D' and MAF_A/MAF_B from the dprime/with-freqs flags). --ld-window-r2 0 keeps every pair (PLINK otherwise drops pairs below r²=0.2), and the --ld-window* flags raise the default limits on how far apart paired SNPs may be. Tune them to the span you want rendered.

dprime also switches r² itself to the haplotype-frequency estimate, so the R2 column of a run with it and a run without it are two different statistics. This is PLINK 1.9; plink2 replaced --r2 with --r2-phased and --r2-unphased.

For regional analyses the plain study.ld file works as-is with PlinkLDAdapter. For chromosome-scale or genome-wide LD, bgzip and tabix the file so only pairs in the visible region are fetched, then use PlinkLDTabixAdapter:

# plink pads its columns with spaces and tabix indexes on tabs, so the awk
# retabs as well as commenting the header. `jbrowse sort-bed` is then
# `sort -k1,1 -k2,2n` under LC_ALL=C with that `#` line kept on top.
awk 'NR == 1 {$1 = "#"$1} {$1 = $1}1' OFS='\t' study.ld |
  jbrowse sort-bed | bgzip > study.sorted.ld.gz

# BP positions in PLINK output are 1-based, matching tabix's default
tabix -s 1 -b 2 -e 2 study.sorted.ld.gz

The # is worth the extra step. tabix keeps a header two ways: commented with the meta character, or counted with -S 1. Only the commented form is what tabix -H prints and what most readers, JBrowse included, ask for first, so a -S 1 file's header is easy for a tool to miss entirely — which costs you the DP column, and with it the option of drawing D' rather than r². Marking the header with -c C makes the meta character C, so every chr1-style data row reads as a comment.

A file already indexed with -S 1 still loads; JBrowse reads the header either way.

GWASAdapter

GWASAdapter reads the bgzipped results from bedGzLocation with a tabix index.location, or from the uri shorthand, which resolves the sibling <file>.tbi. scoreColumn names the header column plotted on the Y axis. See the autogenerated GWASAdapter docs for defaults and the full slot list.

The bgzipped output above ends in .txt.gz, which auto-detects as GWASAdapter in the Add Track dialog. Other extensions such as .bed.gz require manual adapter selection.

LinearManhattanDisplay

On the display:

color sets the point color, a CSS literal or a jexl: expression
colorBy: "ld" colors points by r² to the index SNP, and requires an ldAdapter sub-adapter on the GWASAdapter
scatterPointSize sets the point diameter in px

See the autogenerated LinearManhattanDisplay docs for defaults and the full slot list.

Examples

A minimal track, using the uri shorthand for the tabix index:

Config file CLI (add-track)

{
  "type": "GWASTrack",
  "trackId": "my_gwas",
  "name": "My GWAS",
  "assemblyNames": ["hg38"],
  "adapter": {
    "type": "GWASAdapter",
    "uri": "https://yourhost/results.bed.gz"
  }
}

jbrowse add-track https://yourhost/results.bed.gz \
  --trackId my_gwas \
  --name "My GWAS" \
  --assemblyNames hg38 \
  --adapterType GWASAdapter \
  --trackType GWASTrack

Coloring points by LD to the index SNP. Swap PlinkLDAdapter for PlinkLDTabixAdapter when the .ld file is bgzipped and tabix-indexed:

{
  "type": "GWASTrack",
  "trackId": "sle_gwas",
  "name": "SLE GWAS",
  "assemblyNames": ["hg19"],
  "adapter": {
    "type": "GWASAdapter",
    "uri": "https://yourhost/sle.bed.gz",
    "scoreColumn": "neg_log_pvalue",
    "ldAdapter": {
      "type": "PlinkLDAdapter",
      "uri": "https://yourhost/sle.ld"
    }
  },
  "displayDefaults": {
    "colorBy": "ld"
  }
}

For a per-feature color, set color to a jexl expression such as "jexl:feature.score > 7.3 ? 'red' : '#0068d1'". See the jexl guide, and property access vs get() for when to use the get(feature,'score') form.

GWAS track

Preparing the GWAS file#

Preparing the LD file#

GWASAdapter#

LinearManhattanDisplay#

Examples#

See also#

Preparing the GWAS file

Preparing the LD file

GWASAdapter

LinearManhattanDisplay

Examples

See also