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The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another

Kendler, Kenneth S. ; Ohlsson, Henrik LU ; Sundquist, Jan LU and Sundquist, Kristina LU (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
; ; and
organization
publishing date
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}},
}