The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another
(2024) In Psychological Medicine- Abstract
Background One potential cause of comorbidity is the direct causal effect of one disorder - A - 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 v. without a prior onset of B. Methods In all individuals (n = 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... (More)
Background One potential cause of comorbidity is the direct causal effect of one disorder - A - 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 v. without a prior onset of B. Methods In all individuals (n = 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 v. had not had a prior onset of disorder A. Results In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without v. 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. Conclusions 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.
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- author
- Kendler, Kenneth S. ; Ohlsson, Henrik LU ; Sundquist, Jan LU and Sundquist, Kristina LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- comorbidity, drug use disorder, familial genetic risk scores, major depression, schizophrenia
- in
- Psychological Medicine
- publisher
- Cambridge University Press
- external identifiers
-
- pmid:38314515
- scopus:85184566816
- ISSN
- 0033-2917
- DOI
- 10.1017/S0033291723003847
- language
- English
- LU publication?
- yes
- id
- b8ba11be-4a3d-43e9-be74-ff46b9f056ba
- date added to LUP
- 2024-03-01 12:20:13
- date last changed
- 2024-04-15 00:46:24
@article{b8ba11be-4a3d-43e9-be74-ff46b9f056ba, abstract = {{<p>Background One potential cause of comorbidity is the direct causal effect of one disorder - A - 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 v. without a prior onset of B. Methods In all individuals (n = 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 v. had not had a prior onset of disorder A. Results In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without v. 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. Conclusions 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.</p>}}, author = {{Kendler, Kenneth S. and Ohlsson, Henrik and Sundquist, Jan and Sundquist, Kristina}}, issn = {{0033-2917}}, keywords = {{comorbidity; drug use disorder; familial genetic risk scores; major depression; schizophrenia}}, language = {{eng}}, publisher = {{Cambridge University Press}}, series = {{Psychological Medicine}}, title = {{The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another}}, url = {{http://dx.doi.org/10.1017/S0033291723003847}}, doi = {{10.1017/S0033291723003847}}, year = {{2024}}, }