SLALOM

SLALOM (suspicious loci analysis of meta-analysis summary statistics) is a summary statistics-based QC method that identifies suspicious loci for meta-analysis fine-mapping by detecting association statistics outliers based on local LD structure. SLALOM only takes GWAS summary statistics and ancestry-matched external LD reference (e.g., gnomAD) as input and predicts whether each locus shows a suspicious pattern that called into question fine-mapping accuracy. The outlier detection was built upon the simplified version of the DENTIST method.

Analysis and figure generation code for Kanai, M. et al. (2022) is available here. Fine-mapping pipeline is available here.

Requirements

Python 3.7 or later
Hail v0.2
numpy
scipy
pandas

To run our WDL pipeline on Google Cloud, you additionally need:

Cromwell
Active Google Cloud project
- Note: A part of reference files are located in a public requester-pays bucket (gs://finucane-requester-pays)

To run SLALOM locally, you need:

Cloud Storage Connector

The following command would be the easiest way of installation.

curl -sSL https://broad.io/install-gcs-connector | python3 - --gcs-requester-pays-project YOUR_PROJECT_ID

Usage

(Recommended) WDL pipeline

Please modify wdl/slalom_example.json and submit with wdl/slalom.wdl and wdl/slalom_sub.zip.

Running per-locus

Example files are available at ./example which was created from the GBMI meta-analysis summary statistics for COPD available here.

PYSPARK_SUBMIT_ARGS="--conf spark.driver.memory=1g pyspark-shell" \
python3 slalom.py \
        --snp example/example.snp \
        --out example/example.slalom.txt \
        --out-summary example/example.summary.txt \
        --annotate-consequence \
        --annotate-gnomad-freq \
        --export-r \
        --lead-variant-choice "prob" \
        --weighted-average-r afr=n_afr amr=n_amr eas=n_eas fin=n_fin nfe=n_nfe \
        --dentist-s \
        --abf \
        --summary \
        --case-control \
        --reference-genome GRCh38

Citation

Kanai, M. et al. Meta-analysis fine-mapping is often miscalibrated at single-variant resolution. Cell Genomics 2, 100210 (2022)

Contact

Masahiro Kanai (mkanai@broadinstitute.org)