The typology of common psychiatric disorders as depicted by genetic maps : a study based on Swedish population-based registers
(2026) In World Psychiatry 25(2). p.278-286- Abstract
We sought to clarify the inter-relationships among a range of psychiatric and substance use disorders by employing two-dimensional genetic maps, with axes defined by family genetic risk for major depression (MD) and drug use disorder (DUD). Using comprehensive Swedish national register data, we located cases of 12 disorders within this space and examined how their genetic risk profiles varied as a function of sex, age at onset, and level of recurrence. Disorders segregated robustly into two clusters. Internalizing disorders were characterized by moderate genetic liability for MD and low liability for DUD, while externalizing disorders displayed substantial risk for both genetic dimensions. These patterns were replicated across regions... (More)
We sought to clarify the inter-relationships among a range of psychiatric and substance use disorders by employing two-dimensional genetic maps, with axes defined by family genetic risk for major depression (MD) and drug use disorder (DUD). Using comprehensive Swedish national register data, we located cases of 12 disorders within this space and examined how their genetic risk profiles varied as a function of sex, age at onset, and level of recurrence. Disorders segregated robustly into two clusters. Internalizing disorders were characterized by moderate genetic liability for MD and low liability for DUD, while externalizing disorders displayed substantial risk for both genetic dimensions. These patterns were replicated across regions of Sweden. Post-traumatic stress disorder (PTSD) grouped with the internalizing cluster, whereas borderline personality disorder aligned with the externalizing group. Sex differences in genetic liability were common and frequently involved both axes: typically, the sex with the lower disorder prevalence carried higher genetic risk, with the most striking contrasts observed for alcohol use disorder (AUD) and DUD. Across most disorders, earlier age at onset was associated with elevated genetic liability, with particularly strong effects for AUD, MD and PTSD. Similarly, high level of recurrence consistently indexed increased genetic risk, often spanning both axes, with notable prominence for AUD, DUD, MD and PTSD. Taken together, these findings suggest that the genetic liabilities underlying psychiatric and substance use disorders are not fixed entities but vary systematically with key clinical features. Considering multiple genetic risks simultaneously provides an informative framework for understanding cross-disorder relationships between psychiatric disorders.
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- author
- Kendler, Kenneth S. ; Ohlsson, Henrik LU ; Amstadter, Ananda B. ; Sundquist, Jan LU and Sundquist, Kristina LU
- organization
- publishing date
- 2026-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- age at onset, Common psychiatric disorders, cross-disorder relationships, family genetic risk, genetic maps, level of recurrence, national register data, substance use disorders
- in
- World Psychiatry
- volume
- 25
- issue
- 2
- pages
- 9 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:105039109502
- pmid:42136436
- ISSN
- 1723-8617
- DOI
- 10.1002/wps.70074
- language
- English
- LU publication?
- yes
- id
- e7dc84ea-9543-4a6b-8953-2f46ba6f8fa6
- date added to LUP
- 2026-08-11 14:05:42
- date last changed
- 2026-08-12 03:00:03
@article{e7dc84ea-9543-4a6b-8953-2f46ba6f8fa6,
abstract = {{<p>We sought to clarify the inter-relationships among a range of psychiatric and substance use disorders by employing two-dimensional genetic maps, with axes defined by family genetic risk for major depression (MD) and drug use disorder (DUD). Using comprehensive Swedish national register data, we located cases of 12 disorders within this space and examined how their genetic risk profiles varied as a function of sex, age at onset, and level of recurrence. Disorders segregated robustly into two clusters. Internalizing disorders were characterized by moderate genetic liability for MD and low liability for DUD, while externalizing disorders displayed substantial risk for both genetic dimensions. These patterns were replicated across regions of Sweden. Post-traumatic stress disorder (PTSD) grouped with the internalizing cluster, whereas borderline personality disorder aligned with the externalizing group. Sex differences in genetic liability were common and frequently involved both axes: typically, the sex with the lower disorder prevalence carried higher genetic risk, with the most striking contrasts observed for alcohol use disorder (AUD) and DUD. Across most disorders, earlier age at onset was associated with elevated genetic liability, with particularly strong effects for AUD, MD and PTSD. Similarly, high level of recurrence consistently indexed increased genetic risk, often spanning both axes, with notable prominence for AUD, DUD, MD and PTSD. Taken together, these findings suggest that the genetic liabilities underlying psychiatric and substance use disorders are not fixed entities but vary systematically with key clinical features. Considering multiple genetic risks simultaneously provides an informative framework for understanding cross-disorder relationships between psychiatric disorders.</p>}},
author = {{Kendler, Kenneth S. and Ohlsson, Henrik and Amstadter, Ananda B. and Sundquist, Jan and Sundquist, Kristina}},
issn = {{1723-8617}},
keywords = {{age at onset; Common psychiatric disorders; cross-disorder relationships; family genetic risk; genetic maps; level of recurrence; national register data; substance use disorders}},
language = {{eng}},
number = {{2}},
pages = {{278--286}},
publisher = {{Wiley-Blackwell}},
series = {{World Psychiatry}},
title = {{The typology of common psychiatric disorders as depicted by genetic maps : a study based on Swedish population-based registers}},
url = {{http://dx.doi.org/10.1002/wps.70074}},
doi = {{10.1002/wps.70074}},
volume = {{25}},
year = {{2026}},
}