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Arnold LM, Hudson JI, Hess EV, Ware AE, Fritz DA, Auchenbach MB, Starck LO, Keck PE. Family study of fibromyalgia. Arthritis Rheum. 2004;50(3):944-52. PMID 15022338

One-paragraph summary

Controlled family study testing whether FM and pain sensitivity aggregate in families and whether FM coaggregates with major mood disorder. Probands were 78 FM patients (ACR criteria) and 40 RA controls without lifetime FM, ages 40–55, recruited from two community rheumatology practices; information was collected on 533 relatives of FM probands and 272 relatives of RA probands using dolorimeter tender-point exams, structured clinical interviews, and structured family interviews for unavailable relatives. FM aggregated strongly: the odds of FM in a relative of an FM proband vs a relative of an RA proband were 8.5 (95% CI 2.8–26, p=0.0002). Relatives of FM probands also had more tender points and lower total myalgic scores (i.e., greater pressure-pain sensitivity) regardless of FM status. FM coaggregated with major mood disorder (major depression or bipolar): OR 1.8 (95% CI 1.1–2.9, p=0.013) for mood disorder in relatives of FM vs RA probands.

Key findings

  • OR 8.5 (2.8–26) for FM in first-degree relatives of FM probands vs RA-proband relatives.
  • Objective pressure-pain sensitivity (tender point count up, myalgic score down) aggregates in families independent of FM diagnosis — an endophenotype signal.
  • FM-mood disorder familial coaggregation OR 1.8 (1.1–2.9): shared familial risk factors between FM and mood disorders, not merely reactive depression.
  • Design strengths over prior reports (e.g., Buskila 1997, PMID 9150086): rheumatic-disease control probands, examiner-assessed outcomes, regression adjusted for within-family correlation.

Limitations

  • Probands from specialty referral practices; aggregation may be weaker for community-ascertained FM.
  • RA relatives as comparator could exaggerate ORs if RA families under-report pain (or compress them via pain over-ascertainment in RA families — direction debatable).
  • Family studies cannot separate genes from shared household environment; that required the Swedish twin data (Kato 2006, PMID 16646040).
  • Wide CI (2.8–26); the point estimate is imprecise.

Why it matters

The methodological anchor for FM genetics: it established familial aggregation with an examined, controlled design, put a number on it that motivated the linkage and GWAS programs (λs 13.6 in the follow-on linkage study, PMID 23280346), and pre-figured the FM-mood shared-liability finding that GWAS-era genetic correlations (PMID 42521817) later confirmed at molecular level.

Cited by wiki pages

  • genetics-and-risk-factors
  • comorbidities-and-overlap