Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.
Bos, Martje, Monden, Rei, Wray, Naomi R et al. · Psychological medicine · 2025 · DOI
Quick Summary
This study looked at whether ME/CFS, irritable bowel syndrome, and fibromyalgia run in families, and whether they share common causes with depression and anxiety disorders. Researchers studied over 150,000 people in the Netherlands and found that these conditions do tend to cluster in families—if a relative has one of these conditions, your risk of having it is higher. ME/CFS showed the strongest family connection and was most closely linked to depression.
Why It Matters
This research provides evidence that ME/CFS has a significant heritable and familial component (42% familiality) and is genetically and environmentally linked to psychiatric conditions. Understanding these shared pathways may help explain why ME/CFS and depression co-occur so frequently and could inform more integrated treatment approaches and genetic research strategies.
Observed Findings
ME/CFS showed the highest familiality estimate at 42% (95% CI: 33–50), compared to IBS at 22% (95% CI: 16–29) and fibromyalgia at intermediate levels.
Recurrence risk ratios within disorders ranged from 1.45 to 2.23, indicating first-degree relatives have 1.45–2.23 times higher risk of the same disorder.
The familial correlation between ME/CFS and major depression was +0.83 (95% CI: 0.66–0.99), the highest between any internalizing and functional disorder pair.
Familial correlations between fibromyalgia and agoraphobia were lowest at +0.37 (95% CI: 0.24–0.51).
Cross-disorder familial aggregation (λR 1.17–1.94) indicates relatives of people with one functional disorder have elevated risk of internalizing disorders and vice versa.
Inferred Conclusions
Functional disorders have a clear familial component, with ME/CFS showing the strongest evidence for inheritance or family clustering.
Internalizing disorders and functional disorders share common genetic and/or family-environmental risk factors, suggesting overlapping biological and psychosocial mechanisms.
ME/CFS is most closely related etiologically to internalizing disorders among the three functional disorders studied, supporting the need for integrated psychiatric and somatic research approaches.
Remaining Questions
What specific genetic variants or environmental risk factors are shared between ME/CFS and depression, and do they involve the same biological pathways?
What This Study Does Not Prove
This study does not prove that genes or family environment *cause* ME/CFS or that psychiatric conditions cause ME/CFS—it only shows they aggregate together in families. The observational design cannot establish the direction or mechanism of causality. Additionally, the findings apply to a Dutch population and may not fully generalize to other ethnic or geographic groups.
How much of the familial aggregation is explained by genetic factors versus shared family environment, parenting styles, or modeling of illness behavior?
Do different ME/CFS phenotypes (post-viral, gradual onset, severe cognitive dysfunction) show differential familial correlations with internalizing disorders?
Would results generalize to non-European populations with different genetic backgrounds and cultural attitudes toward functional and psychiatric illness?