{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T01:47:12Z","timestamp":1786499232828,"version":"build-2736575974"},"reference-count":74,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"unspecified","delay-in-days":121,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S003329172500100X_sec28\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>Functional disorders (FDs) are characterized by persistent somatic symptoms and are highly comorbid with internalizing disorders (IDs). To provide much-needed insight into FD etiology, we evaluated FD and ID familial coaggregation and shared familiality.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S003329172500100X_sec29\" sec-type=\"methods\">\n\t    <jats:title>Methods<\/jats:title>\n\t    <jats:p>Lifelines is a three-generation cohort study, which assessed three FDs (myalgic encephalomyelitis\/chronic fatigue syndrome [ME\/CFS], irritable bowel syndrome [IBS], and fibromyalgia [FM]) and six IDs (major depressive disorder [MDD], dysthymia [DYS], generalized anxiety disorder [GAD], agoraphobia [AGPH], social phobia [SPH], and panic disorder [PD]) according to diagnostic criteria. Based on 153,803 individuals, including 90,397 with a first-degree relative in Lifelines, we calculated recurrence risk ratios (\u03bb<jats:sub>R<\/jats:sub>s) and tetrachoric correlations to evaluate familial aggregation and coaggregation of these disorders in first-degree relatives. We then estimated their familiality and familial correlations.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S003329172500100X_sec30\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>Familial aggregation was observed across disorders, with \u03bb<jats:sub>R<\/jats:sub> ranging from 1.45 to 2.23 within disorders and from 1.17 to 1.94 across disorders. Familiality estimates ranged from 22% (95% confidence interval [CI]: 16\u201329) for IBS to 42% (95% CI: 33\u201350) for ME\/CFS. Familial correlations ranged from +0.37 (95% CI: 0.24\u20130.51) between FM and AGPH to +0.97 (95% CI: 0.80\u20131) between ME\/CFS and FM. The highest familial correlation between an ID and FD was +0.83 (95% CI: 0.66\u20130.99) for MDD and ME\/CFS.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S003329172500100X_sec31\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>There is a clear familial component to FDs, which is partially shared with IDs. This suggests that IDs and FDs share both genetic and family-environmental risk factors. Of the FDs, ME\/CFS is most closely related to IDs.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1017\/s003329172500100x","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:50:58Z","timestamp":1746186658000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":6,"title":["Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort"],"prefix":"10.1017","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5288-2223","authenticated-orcid":false,"given":"Martje","family":"Bos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-5447","authenticated-orcid":false,"given":"Rei","family":"Monden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7421-3357","authenticated-orcid":false,"given":"Naomi R.","family":"Wray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-6570","authenticated-orcid":false,"given":"Kenneth S.","family":"Kendler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6393-0032","authenticated-orcid":false,"given":"Judith G. 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