A visualization tool for creating publication-ready lollipop plots of rare variant associations per gene. The plots display genetic variants with their association statistics, protein domains (Pfam), exon structure, allele frequencies, and effect sizes (Beta values).

• Comprehensive Visualization: Shows variants with their genomic positions, association q-values, effect directions (positive/negative Beta), and allele frequencies
• Protein Domain Annotation: Integrates Pfam domain information from Ensembl
• Gene Structure: Displays exon/intron structure with UTRs and coding sequences (CDS)
• Customizable: Configurable q-value thresholds, output formats, and plot dimensions
• Flexible Input: Works with Regenie association studies and can be adapted to other GWAS tools

Create and activate the conda environment with all required dependencies:

conda env create -f environment.yml
conda activate lollipop

If you prefer to install dependencies manually, you'll need R (version 4.1+) with the following packages:

Bioconductor packages:

• biomaRt
• ensembldb
• EnsDb.Hsapiens.v86
• (see environment.yml for complete list)

CRAN packages:

• data.table
• ggplot2
• tidyverse
• ggrepel
• lemon
• stringr
• bedr
• optparse

The tool requires the following input files:

A named list of data frames, where each element corresponds to a gene. Each data frame must contain:

• CHROM: Chromosome
• GENPOS: Genomic position
• ID: Variant identifier
• ALLELE0: Reference allele
• ALLELE1: Alternate allele
• A1FREQ: Alternate allele frequency
• N: Sample size
• TEST: Test name
• BETA: Effect size (Beta coefficient)
• SE: Standard error
• trait: Trait name
• qval: Q-value (multiple-testing corrected p-value)
• variant: Variant in format "chr:pos:ref>alt" (e.g., "19:12896252:G>A")

A named list of data frames with variant functional consequences:

• variant: Variant identifier (matching the variants file)
• consequence: Variant consequence (e.g., "missense_variant", "synonymous_variant", "stop_gained")

Tab-delimited file with transcript annotations containing at minimum:

• ENST: Ensembl transcript ID
• SYMBOL: Gene symbol
• (Additional columns as needed)

Tab-delimited file with exon structure information:

• Transcript ID
• CDS start
• CDS end
• Number of exons
• Exon starts (comma-separated)
• Exon ends (comma-separated)
• Transcript type

Generate a lollipop plot for a specific gene:

Rscript lollipop_maker.R --symbol GCDH

Or using an Ensembl transcript ID:

Rscript lollipop_maker.R --enst ENST00000123456

Customize input files, thresholds, and output:

Rscript lollipop_maker.R \
  --symbol GCDH \
  --variants data/my_variants.rds \
  --annotations data/my_annotations.rds \
  --transcripts data/my_transcripts.tsv.gz \
  --exons data/my_exons.txt.gz \
  --qvalue 1e-5 \
  --output results/ \
  --width 25 \
  --height 10 \
  --dpi 600

Note: Either --symbol or --enst must be provided.

Rscript lollipop_maker.R --help

The tool generates three output files per gene:

1. {SYMBOL}_lolli.png: High-resolution PNG plot
2. {SYMBOL}_lolli.tiff: TIFF format plot (for publications)
3. {SYMBOL}_lolli.tsv: Tab-separated table of variants with annotations and statistics

• Lollipop stems: Represent individual variants at their genomic positions
• Lollipop heads (circles): Size indicates allele frequency
• Y-axis position: Height shows -log10(q-value); positive/negative indicates Beta direction
  • Upper half: Positive Beta (risk-increasing)
  • Lower half: Negative Beta (protective)
• Red dashed line: Q-value significance threshold
• Blue rectangles: Coding sequence (CDS) exons
• Thin rectangles: Untranslated regions (UTRs)
• Colored rectangles at bottom: Pfam protein domains
• Labels: Significant variants (below q-value threshold) are labeled with ID, frequency, trait, and consequence

Using the provided example data:

# Activate conda environment
conda activate lollipop

# Generate plot for GCDH gene
Rscript lollipop_maker.R --symbol GCDH

# Output will be created in plot/ directory:
# - plot/GCDH_lolli.png
# - plot/GCDH_lolli.tiff
# - plot/GCDH_lolli.tsv

While designed for Regenie output, the tool can be adapted for other GWAS tools by:

1. Converting your association results to the required format (see Input Data Requirements)
2. Ensuring variant IDs match between association results and annotations
3. Computing q-values from p-values if not provided (e.g., using the qvalue R package)

If you use this tool in your research, please cite:

R.R. Choudhury (2025). Rare variant GWAS lollipop plots. https://github.com/rimjhimroy/Rare-variant-GWAS-lollipop-plot

Suggested BibTeX for this wrapper:

@misc{rchoudhury_lollipop_plot_2025,
	author = {Choudhury, R. R.},
	title = {Rare variant GWAS lollipop plots},
	year = {2025},
	howpublished = {Repository / workflow in project},
	note = {URL: https://github.com/rimjhimroy/Rare-variant-GWAS-lollipop-plot}
}

MIT License - see LICENSE file for details

For issues, questions, or contributions, please visit: https://github.com/rimjhimroy/Rare-variant-GWAS-lollipop-plot

This tool integrates data from:

• Ensembl (biomaRt)
• Pfam protein domain database
• EnsDb.Hsapiens.v86 annotation package