{
  "id": "SCR-LIP-000235",
  "statement": "This review reports lipedema as polygenic with familial history in 30-89% of cases, citing a 2022 GWAS (130 carriers) identifying 6 regions (CPE, ZNF25, ZNF33A linked to estrogen biology), a UK Biobank study (24,450 women) finding 18 loci replicating VEGFA and GRB14-COBLL1, a partial loss-of-function missense variant in AKR1C1 in a non-syndromic lipedema family, and a multigene panel of 305 loci finding 17 probable deleterious lesions in 21/162 participants, with no single causal gene and no overlap with primary lymphedema or lipodystrophies.",
  "statement_pt": "Esta revisão relata o lipedema como poligênico, com história familiar em 30-89% dos casos, citando um GWAS de 2022 (130 portadoras) que identificou 6 regiões (CPE, ZNF25, ZNF33A ligadas à biologia do estrogênio), um estudo no UK Biobank (24.450 mulheres) que encontrou 18 loci replicando VEGFA e GRB14-COBLL1, uma variante missense de perda parcial de função em AKR1C1 em uma família com lipedema não sindrômico, e um painel multigênico de 305 loci que encontrou 17 lesões deletérias prováveis em 21/162 participantes, sem gene único causal e sem sobreposição com linfedema primário ou lipodistrofias.",
  "claim_type": "clinical_association",
  "context": {
    "population": "—",
    "condition": "lipedema",
    "exposure": "—",
    "comparator": "—",
    "outcome": "—",
    "scope": "auto-ingested from Layer 1 surveillance"
  },
  "knowledge_state": "emerging",
  "evidence_confidence": "moderate",
  "evidence": [
    {
      "ref": "DOI:10.1038/s44324-025-00093-y",
      "stance": "supporting",
      "study_design": "review",
      "n": null,
      "risk_of_bias": "unknown",
      "grade": "very_low",
      "year": 2025,
      "amato_authored": false,
      "note": "The review directly synthesizes genetic findings in lipedema, naming specific GWAS loci, candidate genes, and a missense variant, and characterizes the inheritance as polygenic, directly addressing the question. [grade capped moderate->very_low per curated Oxford N6]",
      "title": "Unraveling lipedema: comprehensive insights and the path to future discoveries",
      "authors": "Faria et al.",
      "journal": "npj Metabolic Health and Disease",
      "_prov": {
        "grade_source": "bib_curated"
      }
    },
    {
      "ref": "DOI:10.1038/s41431-022-01231-6",
      "stance": "supporting",
      "study_design": "cross_sectional",
      "n": null,
      "risk_of_bias": "unknown",
      "grade": "moderate",
      "year": 2023,
      "amato_authored": false,
      "note": "First GWAS of a lipedema phenotype directly identifying specific genetic variants and a polygenic inheritance pattern, with partial replication; uses an inferred phenotype rather than clinical diagnosis in the discovery cohort, limiting cer",
      "title": "Genome-wide association study of a lipedema phenotype among women in the UK Biobank identifies multiple genetic risk factors",
      "authors": "Klimentidis et al.",
      "journal": "European Journal of Human Genetics"
    }
  ],
  "relations": [],
  "gaps": "Auto-ingested single source; not yet human-reviewed.",
  "primary_amato_source": null,
  "curators": [],
  "provenance": {
    "auto": true,
    "engine": "anthropic/claude-opus-4.8",
    "question": "SQ-LIP-000025",
    "source": "library",
    "ingested": "2026-05-31"
  },
  "created": "2026-05-31",
  "updated": "2026-05-31",
  "history": [
    {
      "date": "2026-05-31",
      "event": "created",
      "detail": "auto-ingested for SQ-LIP-000025"
    },
    {
      "date": "2026-05-31",
      "event": "evidence added",
      "detail": "corroborated by DOI:10.1038/s41431-022-01231-6"
    }
  ],
  "license": "CC-BY-4.0",
  "answers_questions": [
    {
      "id": "SQ-LIP-000025",
      "role": "supporting",
      "question": "What specific genetic variants or inheritance patterns have been identified in lipedema?",
      "url": "https://scientificclaims.org/q/SQ-LIP-000025.html"
    }
  ],
  "url": "https://scientificclaims.org/c/SCR-LIP-000235.html"
}