Alterlab Gwas

GWAS Catalog Database

Overview

The GWAS Catalog is a curated repository of published genome-wide association studies maintained by NHGRI and EBI. It contains SNP-trait associations from thousands of GWAS publications — genetic variants, associated traits and diseases, p-values, effect sizes, and full summary statistics for many studies.

Scripts

scripts/query_gwas.py — query the GWAS Catalog REST API (stdlib only, JSON to stdout):

python scripts/query_gwas.py variant rs7903146           # associations for a SNP
python scripts/query_gwas.py trait MONDO_0005148 --size 100  # associations for a trait
python scripts/query_gwas.py study GCST001795            # study metadata

When to Use This Skill

Use this skill for:

• Genetic variant associations — SNPs associated with diseases or traits
• SNP lookups — information about specific variants (rs IDs)
• Trait/disease searches — genetic associations for phenotypes
• Gene associations — variants in or near specific genes
• GWAS summary statistics — complete genome-wide association data
• Study metadata — publication and cohort information
• Population genetics — ancestry-specific associations
• Polygenic risk scores — variants for risk prediction models
• Functional genomics / systematic reviews — variant effects, literature synthesis

Data Model

Four core entities, each with a canonical identifier:

• Studies → GCST accessions (e.g., GCST001234)
• Associations → SNP-trait links with p-values (genome-wide significant: p ≤ 5×10⁻⁸)
• Variants → rs numbers (e.g., rs7903146)
• Traits → trait ontology short-forms (e.g., MONDO_0005148 = type 2 diabetes on the main REST API); genes use HGNC symbols (e.g., TCF7L2)

Trait-ID gotcha (verified): the two APIs disagree on trait IDs. The main REST API has migrated many traits to MONDO / current EFO short-forms, so efoTraits/MONDO_0005148 works but the legacy efoTraits/EFO_0001360 now 404s. The Summary Statistics API still uses the legacy ID: traits/EFO_0001360 works there but traits/MONDO_0005148 404s. If a trait path 404s, look up the current short-form with /efoTraits/search/findByTrait?trait=... (main API) before assuming the trait is absent.

APIs

Two free, no-key REST APIs:

• GWAS Catalog API: https://www.ebi.ac.uk/gwas/rest/api (curated associations, studies, variants, traits)
• Summary Statistics API: https://www.ebi.ac.uk/gwas/summary-statistics/api (all tested variants, not just significant hits)

Core endpoints: /studies/{GCST}, /efoTraits/{efoID}/associations, /singleNucleotidePolymorphisms/{rsID} and /{rsID}/associations. Responses are HAL+JSON with _embedded results, _links for related resources, and pagination (page, size).

Core Workflow

1. Identify the entity — get the EFO ID (trait), rs ID (variant), GCST (study), or HGNC symbol (gene). Use the web interface for free-text → EFO mapping.
2. Query the matching endpoint — trait/variant/study/region; iterate pages via page/size.
3. Filter — by p-value (≤ 5×10⁻⁸ for genome-wide significance), ancestry, sample size, discovery/replication status.
4. Extract — rs IDs, effect alleles/directions, effect sizes (OR or beta), p-values.
5. Cross-reference — Ensembl (consequences), gnomAD (frequencies), Open Targets, PGS Catalog.
6. For genome-wide analyses — pull full summary statistics via the Summary Statistics API or FTP rather than scraping the association endpoints.

Routing Guidance

• Writing API calls / want copy-paste code (endpoints, the four worked examples, summary-stats access, cross-referencing, full paginated Python helper) → references/query_examples.md.
• Following a multi-step task (disease-, variant-, gene-centric, systematic review, summary-stats analysis) or web-interface search syntax → references/query_workflows.md.
• Need response field names, pagination details, or best-practice / data-quality guidance → references/data_fields_and_best_practices.md.
• Deep endpoint specs, all query params, error handling, advanced filtering → references/api_reference.md.

Reference Index

• references/query_examples.md — REST endpoint code, four canonical query examples (disease, variant, summary stats, chromosomal region), summary-statistics access, cross-referencing, and a complete paginated Python integration returning a DataFrame.
• references/query_workflows.md — Five step-by-step query workflows (disease, variant, gene, systematic review, summary statistics) plus web-interface search modes.
• references/data_fields_and_best_practices.md — Association/study response fields, pagination, query and interpretation best practices, rate-limiting ethics, and data-quality considerations.
• references/api_reference.md — Comprehensive endpoint specifications, query parameters/filters, response formats, error handling, and integration with external databases.

Citation and Resources

When using GWAS Catalog data, cite:

• Sollis E, et al. (2023) The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource. Nucleic Acids Research 51:D977-D985. PMID: 36350656. DOI: 10.1093/nar/gkac1010

• Include access date and version when available; cite original studies when discussing specific findings.

• Website: https://www.ebi.ac.uk/gwas/

• Documentation: https://www.ebi.ac.uk/gwas/docs

• API docs: https://www.ebi.ac.uk/gwas/rest/docs/api

• Summary Statistics API: https://www.ebi.ac.uk/gwas/summary-statistics/docs/

• FTP site: http://ftp.ebi.ac.uk/pub/databases/gwas/

• Training materials: https://github.com/EBISPOT/GWAS_Catalog-workshop (Jupyter notebooks, Colab)

• PGS Catalog (polygenic scores): https://www.pgscatalog.org/

• Help and support: gwas-info@ebi.ac.uk