Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases : a twin-sibling study
(2026) In Brain, Behavior, and Immunity 137.- Abstract
Functional somatic syndromes frequently co-occur with internalizing disorders such as anxiety disorders and major depressive disorder. Both show familial associations with immune-mediated diseases. Here, we estimate genetic and environmental contributions to functional somatic syndromes and their overlap with immune-mediated diseases, with internalizing disorders included for comparison. The study sample consisted of 6,097,372 Swedish twins, full siblings, and half-siblings born between 1945 and 2003. From nationwide registers covering inpatient, outpatient and primary care, we extracted ICD diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), major depression,... (More)
Functional somatic syndromes frequently co-occur with internalizing disorders such as anxiety disorders and major depressive disorder. Both show familial associations with immune-mediated diseases. Here, we estimate genetic and environmental contributions to functional somatic syndromes and their overlap with immune-mediated diseases, with internalizing disorders included for comparison. The study sample consisted of 6,097,372 Swedish twins, full siblings, and half-siblings born between 1945 and 2003. From nationwide registers covering inpatient, outpatient and primary care, we extracted ICD diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), major depression, anxiety disorders, and immune-mediated diseases (consisting of autoimmune and autoinflammatory diseases). We used bivariate twin-sibling structural equation modeling to estimate genetic and environmental correlations. We found that the heritability of functional somatic syndromes and internalizing disorders ranged from 15 to 44%, with the unique environment explaining 49–84% of the variance. We estimated the heritability of immune-mediated diseases at 37% (95% CI 36–38%), with a unique environmental component of 63% (95% CI 62–63%). Regarding the genetic correlations with immune-mediated diseases, fibromyalgia showed the strongest genetic correlation (rA = 0.52, 95% CI 0.45–0.63), IBS, ME/CFS, and major depression showed more modest genetic correlations (rA range 0.19–0.29), and anxiety disorders showed minimal genetic correlation (rA = 0.04, 95% CI 0.00–0.08). In summary, fibromyalgia, and to a lesser degree other functional somatic syndromes and major depression, share genetic risk factors with immune-mediated diseases. These findings suggest that immune-related genetic risk factors contribute to the etiology of fibromyalgia and, to a lesser extent, other functional disorders and major depression.
(Less)
- author
- Steen, Olivier D. ; Ohlsson, Henrik LU ; van Ockenburg, Sonja L. ; Kendler, Kenneth S. ; Rosmalen, Judith G.M. ; Sundquist, Kristina LU and van Loo, Hanna M.
- organization
- publishing date
- 2026-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Anxiety disorders, Autoimmune diseases, Chronic, Depressive disorder, Fatigue syndrome, Fibromyalgia, Irritable bowel syndrome
- in
- Brain, Behavior, and Immunity
- volume
- 137
- article number
- 106837
- publisher
- Elsevier
- external identifiers
-
- pmid:42190845
- scopus:105040070292
- ISSN
- 0889-1591
- DOI
- 10.1016/j.bbi.2026.106837
- language
- English
- LU publication?
- yes
- id
- a9caadb7-c65c-43ac-b786-c77aacda0829
- date added to LUP
- 2026-07-03 14:26:32
- date last changed
- 2026-09-11 20:20:08
@article{a9caadb7-c65c-43ac-b786-c77aacda0829,
abstract = {{<p>Functional somatic syndromes frequently co-occur with internalizing disorders such as anxiety disorders and major depressive disorder. Both show familial associations with immune-mediated diseases. Here, we estimate genetic and environmental contributions to functional somatic syndromes and their overlap with immune-mediated diseases, with internalizing disorders included for comparison. The study sample consisted of 6,097,372 Swedish twins, full siblings, and half-siblings born between 1945 and 2003. From nationwide registers covering inpatient, outpatient and primary care, we extracted ICD diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), irritable bowel syndrome (IBS), major depression, anxiety disorders, and immune-mediated diseases (consisting of autoimmune and autoinflammatory diseases). We used bivariate twin-sibling structural equation modeling to estimate genetic and environmental correlations. We found that the heritability of functional somatic syndromes and internalizing disorders ranged from 15 to 44%, with the unique environment explaining 49–84% of the variance. We estimated the heritability of immune-mediated diseases at 37% (95% CI 36–38%), with a unique environmental component of 63% (95% CI 62–63%). Regarding the genetic correlations with immune-mediated diseases, fibromyalgia showed the strongest genetic correlation (rA = 0.52, 95% CI 0.45–0.63), IBS, ME/CFS, and major depression showed more modest genetic correlations (rA range 0.19–0.29), and anxiety disorders showed minimal genetic correlation (rA = 0.04, 95% CI 0.00–0.08). In summary, fibromyalgia, and to a lesser degree other functional somatic syndromes and major depression, share genetic risk factors with immune-mediated diseases. These findings suggest that immune-related genetic risk factors contribute to the etiology of fibromyalgia and, to a lesser extent, other functional disorders and major depression.</p>}},
author = {{Steen, Olivier D. and Ohlsson, Henrik and van Ockenburg, Sonja L. and Kendler, Kenneth S. and Rosmalen, Judith G.M. and Sundquist, Kristina and van Loo, Hanna M.}},
issn = {{0889-1591}},
keywords = {{Anxiety disorders; Autoimmune diseases; Chronic; Depressive disorder; Fatigue syndrome; Fibromyalgia; Irritable bowel syndrome}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Brain, Behavior, and Immunity}},
title = {{Shared genetic risk between functional somatic syndromes, internalizing disorders, and immune-mediated diseases : a twin-sibling study}},
url = {{http://dx.doi.org/10.1016/j.bbi.2026.106837}},
doi = {{10.1016/j.bbi.2026.106837}},
volume = {{137}},
year = {{2026}},
}