{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T13:36:11Z","timestamp":1781962571319,"version":"3.54.5"},"reference-count":43,"publisher":"Cambridge University Press (CUP)","issue":"8","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"unspecified","delay-in-days":0,"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":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0033291723003847_sec_a1\"><jats:title>Background<\/jats:title><jats:p>One potential cause of comorbidity is the direct causal effect of one disorder \u2013 A \u2013 on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with <jats:italic>v.<\/jats:italic> without a prior onset of B.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291723003847_sec_a2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>In all individuals (<jats:italic>n<\/jats:italic> = 905 736) born in Sweden from 1980 to 1990, from six psychiatric and drug use disorders (major depression, anxiety disorders, alcohol use disorder, drug use disorder, bipolar disorder, and schizophrenia), we formed 14 pairs of disorders A and B. In these pairs, we compared, using Cox proportional hazards models, the predictive effect of the familial-genetic risk score (FGRS) for disorder B in those who had <jats:italic>v.<\/jats:italic> had not had a prior onset of disorder A.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291723003847_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without <jats:italic>v.<\/jats:italic> with a prior history of disorder A. These effects were similar across sex, stable across levels of FGRS and not likely due to clinician bias. In many of our disorder pairs, previous clinical studies suggest a mechanism for a causal effect of disorder A on B.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291723003847_sec_a4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide indirect evidence that the occurrence of one psychiatric or substance use disorder often has a causal effect on risk for subsequent disorders. This mechanism may substantially contribute to the widespread comorbidity among psychiatric conditions.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291723003847","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T09:35:24Z","timestamp":1707125724000},"page":"1867-1875","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another"],"prefix":"10.1017","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-6570","authenticated-orcid":false,"given":"Kenneth S.","family":"Kendler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Ohlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sundquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sundquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"S0033291723003847_ref9","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.11.1313"},{"key":"S0033291723003847_ref22","volume-title":"Research in community and mental health","author":"Kessler","year":"1993"},{"key":"S0033291723003847_ref4","doi-asserted-by":"publisher","DOI":"10.1111\/add.15534"},{"key":"S0033291723003847_ref1","first-page":"153","volume-title":"Sources and traditions of classification in psychiatry","author":"Bech","year":"1990"},{"key":"S0033291723003847_ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01454-z"},{"key":"S0033291723003847_ref29","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291706008385"},{"key":"S0033291723003847_ref30","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.6.651"},{"key":"S0033291723003847_ref10","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721005535"},{"key":"S0033291723003847_ref12","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721003354"},{"key":"S0033291723003847_ref5","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291706009135"},{"key":"S0033291723003847_ref28","doi-asserted-by":"publisher","DOI":"10.1177\/003591576005301214"},{"key":"S0033291723003847_ref6","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.2138"},{"key":"S0033291723003847_ref11","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17111251"},{"key":"S0033291723003847_ref2","doi-asserted-by":"publisher","DOI":"10.1080\/15622975.2022.2038797"},{"key":"S0033291723003847_ref3","doi-asserted-by":"publisher","DOI":"10.1080\/08039480500360906"},{"key":"S0033291723003847_ref13","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.18101217"},{"key":"S0033291723003847_ref25","first-page":"19","volume-title":"Basic issues in psychopathology","author":"Klein","year":"1993"},{"key":"S0033291723003847_ref31","first-page":"935","article-title":"Models of comorbidity for multifactorial disorders","volume":"57","author":"Neale","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"S0033291723003847_ref37","unstructured":"SAS Institute, I. 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