{
  "schema_version": "2.0.0",
  "harmonisation_ruleset": "pais-harmony-v1",
  "id": "long-covid-host-genetics",
  "name": "Long COVID Host Genetics Initiative GWAS",
  "aliases": ["Long COVID GWAS (Lammi et al.)", "Long COVID Host Genetics Initiative"],
  "outbreak_event": "COVID-19 pandemic",
  "pathogen_id": "sars-cov-2",
  "pathogen_class": "virus",
  "exposure_ascertainment": "mixed",
  "design": "registry_linkage",
  "denominator_defined": "yes",
  "denominator_method": "Genome-wide meta-analysis of up to 6,450 long COVID cases vs 1,093,995 population controls across 24 studies in 16 countries, with independent replication in 9,500 cases and 798,835 controls.",
  "recruitment_source": "population_registry",
  "time_zero_definition": "Germline genotype (fixed at conception); long COVID caseness ascertained after SARS-CoV-2 infection",
  "time_zero_precision": "undefined",
  "control_group": "unexposed_unmatched",
  "control_matching_variables": ["genetic ancestry"],
  "n_source_population": null,
  "n_enrolled": 6450,
  "n_analysed": 6450,
  "followups": [],
  "max_followup_months": null,
  "instruments": [],
  "case_definition": "who_pcc_2021",
  "pem_assessed": "no",
  "objective_measures": ["none"],
  "specimens_collected": true,
  "specimen_types": ["whole_blood", "saliva"],
  "acute_phase_specimens": "no",
  "storage": null,
  "biobank_status": "active",
  "consent_future_use": "broad",
  "external_access": "open_application",
  "contact": null,
  "registration_id": null,
  "funders": ["COVID-19 Host Genetics Initiative partners"],
  "conflicts": null,
  "data_availability": "GWAS summary statistics released by the COVID-19 Host Genetics Initiative.",
  "notes": "The first genome-wide significant host-genetic association for long COVID: the FOXP4 locus (rs9367106, OR ~1.65), independent of FOXP4's known association with severe acute COVID-19 and replicated in an independent sample. FOXP4 acts in lung morphogenesis and respiratory-epithelial immunity. A consortium meta-analysis rather than a single followed cohort; genetic factors are temporality-valid by construction.",
  "symptom_inventory_scope": "none",
  "n_symptoms_queried": null,
  "symptom_instrument_note": null,
  "related_cohorts": [
    { "id": "recover-adult-long-covid", "relation": "overlapping_population" }
  ],
  "flags": [],
  "last_verified": "2026-07-20",
  "verified_by": "OSMF research-tracker (web-verified against source)",
  "publications": [
    {
      "id": "lammi-2025",
      "title": "Genome-wide association study of long COVID",
      "authors": "Lammi V, et al. (Long COVID Host Genetics Initiative)",
      "year": 2025,
      "journal": "Nature Genetics",
      "type": "journal",
      "doi": "10.1038/s41588-025-02100-w",
      "url": "https://www.nature.com/articles/s41588-025-02100-w",
      "open_access": true,
      "is_primary_cohort_paper": true
    }
  ],
  "observations": [],
  "predictors": [
    {
      "id": "lcgwas-pred-foxp4",
      "cohort_id": "long-covid-host-genetics",
      "publication_id": "lammi-2025",
      "question_type": "conversion",
      "factor_id": "gene:foxp4-locus",
      "factor_verbatim": "FOXP4 locus lead variant rs9367106 risk allele",
      "measurement_window": "genetic_fixed",
      "factor_value_type": "binary",
      "contrast": "rs9367106 risk allele vs reference (per-allele)",
      "reference_level": "reference allele",
      "outcome_measure_id": "case-def:long-covid",
      "outcome_timepoint_months": null,
      "estimate": { "type": "or", "value": 1.65, "ci_low": null, "ci_high": null, "p_value": null, "direction": "increases_risk", "significant": true },
      "model": { "type": "mixed_effects", "adjusted_for": ["genetic principal components", "severe acute COVID-19 signal"], "prespecified": "yes", "n_predictors_tested": null, "multiplicity_correction": "other" },
      "n_analysed": 6450,
      "analysis_status": "analysed",
      "harmonised": null,
      "provenance": { "source_locator": "Results (FOXP4 rs9367106, OR 1.65; genome-wide significant, replicated, independent of severe-COVID signal)", "extracted_by": "OSMF", "extracted_on": "2026-07-20", "verified_by": "OSMF research-tracker", "verified_on": "2026-07-20", "extraction_method": "manual" }
    }
  ],
  "estimates_status": "none"
}