Distance-based signal identification

Usage

qtlFinder(
  d,
  Chromosome = "Chromosome",
  Position = "Position",
  MarkerName = "MarkerName",
  Allele1 = "Allele1",
  Allele2 = "Allele2",
  EAF = "Freq1",
  Effect = "Effect",
  StdErr = "StdErr",
  log10P = "log10P",
  N = "N",
  radius = 1e+06,
  collapse.hla = TRUE,
  build = "hg19"
)

Arguments

d: Input data frame containing summary association statistics.
Chromosome: Chromosome column.
Position: Genomic position column (bp).
MarkerName: Variant identifier (e.g. rsID or SNP ID).
Allele1: Effect allele.
Allele2: Other allele.
EAF: Effect allele frequency.
Effect: Effect estimate.
StdErr: Standard error of the effect estimate.
log10P: Column containing log10(P) values, typically as produced by METAL. Values are converted internally to -log10(P) for ranking signals.
N: Sample size.
radius: Maximum gap (bp) allowed between consecutive variants when defining a locus.
collapse.hla: Logical flag indicating whether variants within the HLA region should be collapsed.
build: Genome build used to define HLA boundaries ("hg19" or "hg38").

Value

A tibble containing one lead variant per non-overlapping genomic locus.

Loci are defined by single-linkage clustering of variants separated by at most radius base pairs. Each locus is represented by its most significant variant (largest -log10(P)).

Output columns

chrom: chromosome
start, end: position of the lead variant
rsid: variant identifier
a1, a2: effect and other allele
EAF: effect allele frequency
b: effect size
SE: standard error
mlog10p: -log10(P) used for ranking
n: sample size
regionStart, regionEnd: boundaries of the merged locus

Notes

Each row corresponds to a non-overlapping locus defined using valr::bed_merge(max_dist = radius).

The lead variant is selected as the SNP with the highest mlog10p.

Details

Variants are merged into non-overlapping loci using valr::bed_merge(max_dist = radius). Variants connected through a chain of gaps less than or equal to radius belong to the same locus.

The most significant variant (largest -log10(P)) within each merged locus is selected as the lead signal.

When collapse.hla=TRUE, signals within the HLA region are collapsed using HLA boundaries:

hg19/GRCh37: chr6:28477797-33448354
hg38/GRCh38: chr6:28510020-33480577