Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study
Abstract Background Functional disorders share familial risk with internalizing disorders such as generalized anxiety disorder and depression, and are comorbid with cardiometabolic and immune-related diseases. We investigated whether functional and internalizing disorders co-aggregate with these dis...
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BMC
2025-08-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-025-04293-7 |
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| author | Olivier D. Steen Martje Bos Sonja L. van Ockenburg Yiling Zhou Ilja M. Nolte Harold Snieder Kenneth Kendler Judith G. M. Rosmalen Hanna M. van Loo |
| author_facet | Olivier D. Steen Martje Bos Sonja L. van Ockenburg Yiling Zhou Ilja M. Nolte Harold Snieder Kenneth Kendler Judith G. M. Rosmalen Hanna M. van Loo |
| author_sort | Olivier D. Steen |
| collection | DOAJ |
| description | Abstract Background Functional disorders share familial risk with internalizing disorders such as generalized anxiety disorder and depression, and are comorbid with cardiometabolic and immune-related diseases. We investigated whether functional and internalizing disorders co-aggregate with these diseases in families to gain insight into the aetiology of functional and internalizing disorders. Methods We included 166,774 subjects (aged 3–94), from the population-based Lifelines Cohort Study, a Dutch general population cohort. We defined cases for three functional disorders (myalgic encephalomyelitis/chronic fatigue syndrome; ME/CFS, fibromyalgia, and irritable bowel syndrome; IBS), two internalizing disorders (major depressive disorder; MDD and generalized anxiety disorder; GAD), cardiometabolic diseases (obesity, metabolic associated steatotic liver disease, type 2 diabetes, hypertension and cardiovascular disease) and immune-related diseases (composite measures of auto-immune disease and atopy). We used logistic regression to model the prevalence of these disorders in the general population and in participants with affected relatives. Using these prevalence estimates, we assessed familial co-aggregation with (1) recurrence risk ratios (λ R ), and (2) familial correlations (r f ). Results All functional and internalizing disorders co-aggregated with immune-related diseases (λ R range 1.06–1.24). ME/CFS, FM, and MDD co-aggregated with most cardiometabolic diseases (λ R range 1.00–1.23). MDD, fibromyalgia, and ME/CFS showed similar familial correlation patterns with both disease groups (r f range 0.12–0.44), while patterns of IBS and GAD were more variable. Conclusions Internalizing and functional disorders share familial risk with immune-related and cardiometabolic diseases. This suggests that risk factors relevant to immune-related and cardiometabolic diseases may also be relevant for FDs. Future studies should investigate such risk factors to identify novel treatment targets. |
| format | Article |
| id | doaj-art-b77e659c31444fcab552e450caefb8fc |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj-art-b77e659c31444fcab552e450caefb8fc2025-08-20T03:46:09ZengBMCBMC Medicine1741-70152025-08-0123111110.1186/s12916-025-04293-7Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort studyOlivier D. Steen0Martje Bos1Sonja L. van Ockenburg2Yiling Zhou3Ilja M. Nolte4Harold Snieder5Kenneth Kendler6Judith G. M. Rosmalen7Hanna M. van Loo8Department of Psychiatry, University of Groningen, University Medical Center GroningenDepartment of Psychiatry, University of Groningen, University Medical Center GroningenDepartment of Internal Medicine, University of Groningen, University Medical Center GroningenDepartment of Epidemiology, University of Groningen, University Medical Center GroningenDepartment of Epidemiology, University of Groningen, University Medical Center GroningenDepartment of Epidemiology, University of Groningen, University Medical Center GroningenVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth UniversityDepartment of Psychiatry, University of Groningen, University Medical Center GroningenDepartment of Psychiatry, University of Groningen, University Medical Center GroningenAbstract Background Functional disorders share familial risk with internalizing disorders such as generalized anxiety disorder and depression, and are comorbid with cardiometabolic and immune-related diseases. We investigated whether functional and internalizing disorders co-aggregate with these diseases in families to gain insight into the aetiology of functional and internalizing disorders. Methods We included 166,774 subjects (aged 3–94), from the population-based Lifelines Cohort Study, a Dutch general population cohort. We defined cases for three functional disorders (myalgic encephalomyelitis/chronic fatigue syndrome; ME/CFS, fibromyalgia, and irritable bowel syndrome; IBS), two internalizing disorders (major depressive disorder; MDD and generalized anxiety disorder; GAD), cardiometabolic diseases (obesity, metabolic associated steatotic liver disease, type 2 diabetes, hypertension and cardiovascular disease) and immune-related diseases (composite measures of auto-immune disease and atopy). We used logistic regression to model the prevalence of these disorders in the general population and in participants with affected relatives. Using these prevalence estimates, we assessed familial co-aggregation with (1) recurrence risk ratios (λ R ), and (2) familial correlations (r f ). Results All functional and internalizing disorders co-aggregated with immune-related diseases (λ R range 1.06–1.24). ME/CFS, FM, and MDD co-aggregated with most cardiometabolic diseases (λ R range 1.00–1.23). MDD, fibromyalgia, and ME/CFS showed similar familial correlation patterns with both disease groups (r f range 0.12–0.44), while patterns of IBS and GAD were more variable. Conclusions Internalizing and functional disorders share familial risk with immune-related and cardiometabolic diseases. This suggests that risk factors relevant to immune-related and cardiometabolic diseases may also be relevant for FDs. Future studies should investigate such risk factors to identify novel treatment targets. https://doi.org/10.1186/s12916-025-04293-7FibromyalgiaMyalgic encephalomyelitis/chronic fatigue syndromeIrritable bowel syndromeAetiologyFamilial co-aggregationCardiometabolic |
| spellingShingle | Olivier D. Steen Martje Bos Sonja L. van Ockenburg Yiling Zhou Ilja M. Nolte Harold Snieder Kenneth Kendler Judith G. M. Rosmalen Hanna M. van Loo Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study BMC Medicine Fibromyalgia Myalgic encephalomyelitis/chronic fatigue syndrome Irritable bowel syndrome Aetiology Familial co-aggregation Cardiometabolic |
| title | Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study |
| title_full | Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study |
| title_fullStr | Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study |
| title_full_unstemmed | Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study |
| title_short | Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study |
| title_sort | functional and internalizing disorders co aggregate with cardiometabolic and immune related diseases within families a population based cohort study |
| topic | Fibromyalgia Myalgic encephalomyelitis/chronic fatigue syndrome Irritable bowel syndrome Aetiology Familial co-aggregation Cardiometabolic |
| url | https://doi.org/10.1186/s12916-025-04293-7 |
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