E2 ModerateModerate confidencePEM ?ObservationalPeer-reviewedMachine draft
Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study.
Steen, Olivier D, Bos, Martje, van Ockenburg, Sonja L et al. · BMC medicine · 2025 · DOI
Quick Summary
This study found that ME/CFS, fibromyalgia, and irritable bowel syndrome tend to run in families alongside conditions like depression, anxiety, autoimmune diseases, and metabolic disorders. Researchers analyzed data from over 166,000 people in a Dutch population cohort to understand whether these conditions share common inherited risk factors. The findings suggest that the causes of functional disorders like ME/CFS may overlap with the causes of immune and metabolic diseases, which could point to new treatment approaches.
Why It Matters
This is one of the first large-scale studies demonstrating that ME/CFS shares familial risk factors with both immune-related and cardiometabolic diseases, strengthening the biological basis for understanding ME/CFS as part of a broader disease network. The findings support the hypothesis that systemic mechanisms underlying immune dysfunction and metabolic abnormalities may be relevant to ME/CFS pathology, opening avenues for investigating shared biological pathways and identifying novel therapeutic targets.
Observed Findings
- All functional and internalizing disorders co-aggregated with immune-related diseases, with recurrence risk ratios ranging from 1.06 to 1.24.
- ME/CFS, fibromyalgia, and major depressive disorder showed co-aggregation with most cardiometabolic diseases (recurrence risk ratios 1.00–1.23).
- ME/CFS, fibromyalgia, and major depressive disorder displayed similar familial correlation patterns with both immune-related and cardiometabolic disease groups (rf 0.12–0.44).
- Familial correlation patterns for IBS and generalized anxiety disorder were more variable and less consistent across disease groups.
- Immunosuppression and metabolic dysfunction appear to cluster within families alongside functional and internalizing disorders.
Inferred Conclusions
- Functional and internalizing disorders share familial risk factors with immune-related and cardiometabolic diseases, suggesting overlapping inherited susceptibility.
- Risk factors relevant to immune dysfunction and metabolic disease may also be relevant to the pathogenesis of functional disorders like ME/CFS.
- Shared biological pathways involving immune regulation and metabolic homeostasis warrant investigation as potential treatment targets for ME/CFS and related conditions.
- The pattern of familial co-aggregation suggests that ME/CFS, fibromyalgia, and depression may represent different phenotypic expressions of shared underlying biological dysfunction.
What This Study Does Not Prove
This study demonstrates familial co-aggregation but does not establish causation or direction of causation between these conditions. It does not identify which specific genetic or environmental factors are shared, nor does it confirm whether ME/CFS causes cardiometabolic disease or vice versa. Self-reported diagnoses without systematic clinical confirmation may have introduced misclassification bias that could affect the strength of observed associations.
Tags
Method Flag:PEM Not DefinedWeak Case DefinitionMixed Cohort