GWAS Catalog Database

Overview

The GWAS Catalog is a comprehensive repository of published genome-wide association studies maintained by the National Human Genome Research Institute (NHGRI) and the European Bioinformatics Institute (EBI). The catalog contains curated SNP-trait associations from thousands of GWAS publications, including genetic variants, associated traits and diseases, p-values, effect sizes, and full summary statistics for many studies.

When to Use This Skill

This skill should be used when queries involve:

• Genetic variant associations: Finding SNPs associated with diseases or traits
• SNP lookups: Retrieving information about specific genetic variants (rs IDs)
• Trait/disease searches: Discovering genetic associations for phenotypes
• Gene associations: Finding variants in or near specific genes
• GWAS summary statistics: Accessing complete genome-wide association data
• Study metadata: Retrieving publication and cohort information
• Population genetics: Exploring ancestry-specific associations
• Polygenic risk scores: Identifying variants for risk prediction models
• Functional genomics: Understanding variant effects and genomic context
• Systematic reviews: Comprehensive literature synthesis of genetic associations

Core Capabilities

1. Understanding GWAS Catalog Data Structure

The GWAS Catalog is organized around four core entities:

• Studies: GWAS publications with metadata (PMID, author, cohort details)
• Associations: SNP-trait associations with statistical evidence (p ≤ 5×10⁻⁸)
• Variants: Genetic markers (SNPs) with genomic coordinates and alleles
• Traits: Phenotypes and diseases (mapped to EFO ontology terms)

Key Identifiers:

• Study accessions: GCST IDs (e.g., GCST001234)
• Variant IDs: rs numbers (e.g., rs7903146) or variant_id format
• Trait IDs: EFO terms (e.g., EFO_0001360 for type 2 diabetes)
• Gene symbols: HGNC approved names (e.g., TCF7L2)

2. Web Interface Searches

The web interface at https://www.ebi.ac.uk/gwas/ supports multiple search modes:

By Variant (rs ID):

rs7903146

Returns all trait associations for this SNP.

By Disease/Trait:

type 2 diabetes
Parkinson disease
body mass index

Returns all associated genetic variants.

By Gene:

APOE
TCF7L2

Returns variants in or near the gene region.

By Chromosomal Region:

10:114000000-115000000

Returns variants in the specified genomic interval.

By Publication:

PMID:20581827
Author: McCarthy MI
GCST001234

Returns study details and all reported associations.

3. REST API Access

The GWAS Catalog provides two REST APIs for programmatic access:

Base URLs:

• GWAS Catalog API: https://www.ebi.ac.uk/gwas/rest/api
• Summary Statistics API: https://www.ebi.ac.uk/gwas/summary-statistics/api

API Documentation:

• Main API docs: https://www.ebi.ac.uk/gwas/rest/docs/api
• Summary stats docs: https://www.ebi.ac.uk/gwas/summary-statistics/docs/

Core Endpoints:

• Studies endpoint - /studies/{accessionID}

import requests

   # Get a specific study
   url = "https://www.ebi.ac.uk/gwas/rest/api/studies/GCST001795"
   response = requests.get(url, headers={"Content-Type": "application/json"})
   study = response.json()

• Associations endpoint - /associations

# Find associations for a variant
   variant = "rs7903146"
   url = f"https://www.ebi.ac.uk/gwas/rest/api/singleNucleotidePolymorphisms/{variant}/associations"
   params = {"projection": "associationBySnp"}
   response = requests.get(url, params=params, headers={"Content-Type": "application/json"})
   associations = response.json()

• Variants endpoint - /singleNucleotidePolymorphisms/{rsID}

# Get variant details
   url = "https://www.ebi.ac.uk/gwas/rest/api/singleNucleotidePolymorphisms/rs7903146"
   response = requests.get(url, headers={"Content-Type": "application/json"})
   variant_info = response.json()

• Traits endpoint - /efoTraits/{efoID}

# Get trait information
   url = "https://www.ebi.ac.uk/gwas/rest/api/efoTraits/EFO_0001360"
   response = requests.get(url, headers={"Content-Type": "application/json"})
   trait_info = response.json()

4. Query Examples and Patterns

Example 1: Find all associations for a disease

import requests

trait = "EFO_0001360"  # Type 2 diabetes
base_url = "https://www.ebi.ac.uk/gwas/rest/api"

# Query associations for this trait
url = f"{base_url}/efoTraits/{trait}/associations"
response = requests.get(url, headers={"Content-Type": "application/json"})
associations = response.json()

# Process results
for assoc in associations.get('_embedded', {}).get('associations', []):
    variant = assoc.get('rsId')
    pvalue = assoc.get('pvalue')
    risk_allele = assoc.get('strongestAllele')
    print(f"{variant}: p={pvalue}, risk allele={risk_allele}")

Example 2: Get variant information and all trait associations

import requests

variant = "rs7903146"
base_url = "https://www.ebi.ac.uk/gwas/rest/api"

# Get variant details
url = f"{base_url}/singleNucleotidePolymorphisms/{variant}"
response = requests.get(url, headers={"Content-Type": "application/json"})
variant_data = response.json()

# Get all associations for this variant
url = f"{base_url}/singleNucleotidePolymorphisms/{variant}/associations"
params = {"projection": "associationBySnp"}
response = requests.get(url, params=params, headers={"Content-Type": "application/json"})
associations = response.json()

# Extract trait names and p-values
for assoc in associations.get('_embedded', {}).get('associations', []):
    trait = assoc.get('efoTrait')
    pvalue = assoc.get('pvalue')
    print(f"Trait: {trait}, p-value: {pvalue}")

Example 3: Access summary statistics

import requests

# Query summary statistics API
base_url = "https://www.ebi.ac.uk/gwas/summary-statistics/api"

# Find associations by trait with p-value threshold
trait = "EFO_0001360"  # Type 2 diabetes
p_upper = "0.000000001"  # p < 1e-9
url = f"{base_url}/traits/{trait}/associations"
params = {
    "p_upper": p_upper,
    "size": 100  # Number of results
}
response = requests.get(url, params=params)
results = response.json()

# Process genome-wide significant hits
for hit in results.get('_embedded', {}).get('associations', []):
    variant_id = hit.get('variant_id')
    chromosome = hit.get('chromosome')
    position = hit.get('base_pair_location')
    pvalue = hit.get('p_value')
    print(f"{chromosome}:{position} ({variant_id}): p={pvalue}")

Example 4: Query by chromosomal region

import requests

# Find variants in a specific genomic region
chromosome = "10"
start_pos = 114000000
end_pos = 115000000

base_url = "https://www.ebi.ac.uk/gwas/rest/api"
url = f"{base_url}/singleNucleotidePolymorphisms/search/findByChromBpLocationRange"
params = {
    "chrom": chromosome,
    "bpStart": start_pos,
    "bpEnd": end_pos
}
response = requests.get(url, params=params, headers={"Content-Type": "application/json"})
variants_in_region = response.json()

5. Working with Summary Statistics

The GWAS Catalog hosts full summary statistics for many studies, providing access to all tested variants (not just genome-wide significant hits).

Access Methods:

• FTP download: http://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/
• REST API: Query-based access to summary statistics
• Web interface: Browse and download via the website

Summary Statistics API Features:

• Filter by chromosome, position, p-value
• Query specific variants across studies
• Retrieve effect sizes and allele frequencies
• Access harmonized and standardized data

Example: Download summary statistics for a study

import requests
import gzip

# Get available summary statistics
base_url = "https://www.ebi.ac.uk/gwas/summary-statistics/api"
url = f"{base_url}/studies/GCST001234"
response = requests.get(url)
study_info = response.json()

# Download link is provided in the response
# Alternatively, use FTP:
# ftp://ftp.ebi.ac.uk/pub/databases/gwas/summary_statistics/GCSTXXXXXX/

6. Data Integration and Cross-referencing

The GWAS Catalog provides links to external resources:

Genomic Databases:

• Ensembl: Gene annotations and variant consequences
• dbSNP: Variant identifiers and population frequencies
• gnomAD: Population allele frequencies

Functional Resources:

• Open Targets: Target-disease associations
• PGS Catalog: Polygenic risk scores
• UCSC Genome Browser: Genomic context

Phenotype Resources:

• EFO (Experimental Factor Ontology): Standardized trait terms
• OMIM: Disease gene relationships
• Disease Ontology: Disease hierarchies

Following Links in API Responses:

import requests

# API responses include _links for related resources
response = requests.get("https://www.ebi.ac.uk/gwas/rest/api/studies/GCST001234")
study = response.json()

# Follow link to associations
associations_url = study['_links']['associations']['href']
associations_response = requests.get(associations_url)

Query Workflows

Workflow 1: Exploring Genetic Associations for a Disease

• Identify the trait using EFO terms or free text:

- Search web interface for disease name

- Note the EFO ID (e.g., EFO_0001360 for type 2 diabetes)

• Query associations via API:

url = f"https://www.ebi.ac.uk/gwas/rest/api/efoTraits/{efo_id}/associations"

• Filter by significance and population:

- Check p-values (genome-wide significant: p ≤ 5×10⁻⁸)

- Review ancestry information in study metadata

- Filter by sample size or discovery/replication status

• Extract variant details:

- rs IDs for each association

- Effect alleles and directions

- Effect sizes (odds ratios, beta coefficients)

- Population allele frequencies

• Cross-reference with other databases:

- Look up variant consequences in Ensembl

- Check population frequencies in gnomAD

- Explore gene function and pathways

Workflow 2: Investigating a Specific Genetic Variant

• Query the variant:

url = f"https://www.ebi.ac.uk/gwas/rest/api/singleNucleotidePolymorphisms/{rs_id}"

• Retrieve all trait associations:

url = f"https://www.ebi.ac.uk/gwas/rest/api/singleNucleotidePolymorphisms/{rs_id}/associations"

• Analyze pleiotropy:

- Identify all traits associated with this variant

- Review effect directions across traits

- Look for shared biological pathways

• Check genomic context:

- Determine nearby genes

- Identify if variant is in coding/regulatory regions

- Review linkage disequilibrium with other variants

Workflow 3: Gene-Centric Association Analysis

• Search by gene symbol in web interface or:

url = f"https://www.ebi.ac.uk/gwas/rest/api/singleNucleotidePolymorphisms/search/findByGene"
   params = {"geneName": gene_symbol}

• Retrieve variants in gene region:

- Get chromosomal coordinates for gene

- Query variants in region

- Include promoter and regulatory regions (extend boundaries)

• Analyze association patterns:

- Identify traits associated with variants in this gene

- Look for consistent associations across studies

- Review effect sizes and directions

• Functional interpretation:

- Determine variant consequences (missense, regulatory, etc.)

- Check expression QTL (eQTL) data

- Review pathway and network context

Workflow 4: Systematic Review of Genetic Evidence

• Define research question:

- Specific trait or disease of interest

- Population considerations

- Study design requirements

• Comprehensive variant extraction:

- Query all associations for trait

- Set significance threshold

- Note discovery and repl