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The outcome of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity

Kendler, Kenneth S. ; Ohlsson, Henrik LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2025) In Psychological Medicine 55.
Abstract

Background We investigate whether, in Swedish national registers, social and psychiatric outcomes for six major psychiatric and substance disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), anxiety disorder (AD), and schizophrenia (SZ) - reflect the primary genetic risk for each disorder and the level of genetic heterogeneity. Methods We utilize Genetic Risk Ratios - defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder - derived from Family Genetic Risk Scores. Poor social outcome was defined by a common factor of four variables: receipt of social welfare, sick leave, early retirement pension, and residence in a socially... (More)

Background We investigate whether, in Swedish national registers, social and psychiatric outcomes for six major psychiatric and substance disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), anxiety disorder (AD), and schizophrenia (SZ) - reflect the primary genetic risk for each disorder and the level of genetic heterogeneity. Methods We utilize Genetic Risk Ratios - defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder - derived from Family Genetic Risk Scores. Poor social outcome was defined by a common factor of four variables: receipt of social welfare, sick leave, early retirement pension, and residence in a socially deprived area. Psychiatric outcome was defined as days of inpatient psychiatric hospitalization. Results With poorer social outcomes, the primary genetic risks rose robustly for all disorders except SZ, as did the secondary genetic risks for DUD, AUD, and attention-deficit hyperactivity disorder. With poorer psychiatric outcomes, available only for BD and SZ, the primary genetic risks increased sharply. Overall, MD, AD, and BD became substantially more genetically heterogenous as their social outcomes became poorer, while for AUD, DUD, and SZ, the increase in heterogeneity was more modest. By contrast, with poorer psychiatric outcome, genetic risks for SZ became substantially more genetically homogeneous, with a similar but less robust trend seen for BD. Conclusions Despite important differences between our primary disorders, social and psychiatric outcomes are often robust indices of genetic risk and can reflect the levels of genetic heterogeneity.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
anxiety disorders, bipolar disorder, genetic heterogeneity, genetic risk, psychiatric outcomes, schizophrenia, social outcomes, substance use disorders
in
Psychological Medicine
volume
55
article number
e233
publisher
Cambridge University Press
external identifiers
  • scopus:105013492748
  • pmid:40810310
ISSN
0033-2917
DOI
10.1017/S0033291725101116
language
English
LU publication?
yes
id
3b906796-ba2c-4855-ac49-724f1eefe3d6
date added to LUP
2025-11-05 15:04:12
date last changed
2025-11-19 16:12:50
@article{3b906796-ba2c-4855-ac49-724f1eefe3d6,
  abstract     = {{<p>Background We investigate whether, in Swedish national registers, social and psychiatric outcomes for six major psychiatric and substance disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), anxiety disorder (AD), and schizophrenia (SZ) - reflect the primary genetic risk for each disorder and the level of genetic heterogeneity. Methods We utilize Genetic Risk Ratios - defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder - derived from Family Genetic Risk Scores. Poor social outcome was defined by a common factor of four variables: receipt of social welfare, sick leave, early retirement pension, and residence in a socially deprived area. Psychiatric outcome was defined as days of inpatient psychiatric hospitalization. Results With poorer social outcomes, the primary genetic risks rose robustly for all disorders except SZ, as did the secondary genetic risks for DUD, AUD, and attention-deficit hyperactivity disorder. With poorer psychiatric outcomes, available only for BD and SZ, the primary genetic risks increased sharply. Overall, MD, AD, and BD became substantially more genetically heterogenous as their social outcomes became poorer, while for AUD, DUD, and SZ, the increase in heterogeneity was more modest. By contrast, with poorer psychiatric outcome, genetic risks for SZ became substantially more genetically homogeneous, with a similar but less robust trend seen for BD. Conclusions Despite important differences between our primary disorders, social and psychiatric outcomes are often robust indices of genetic risk and can reflect the levels of genetic heterogeneity.</p>}},
  author       = {{Kendler, Kenneth S. and Ohlsson, Henrik and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{0033-2917}},
  keywords     = {{anxiety disorders; bipolar disorder; genetic heterogeneity; genetic risk; psychiatric outcomes; schizophrenia; social outcomes; substance use disorders}},
  language     = {{eng}},
  publisher    = {{Cambridge University Press}},
  series       = {{Psychological Medicine}},
  title        = {{The outcome of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity}},
  url          = {{http://dx.doi.org/10.1017/S0033291725101116}},
  doi          = {{10.1017/S0033291725101116}},
  volume       = {{55}},
  year         = {{2025}},
}