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The moderation of genetic risk for ten major psychiatric and substance use disorders by the genetic aptitude for educational attainment

Kendler, Kenneth S. LU ; Ohlsson, Henrik LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2025) In Molecular Psychiatry 30(7). p.3160-3167
Abstract

We seek to clarify the impact of the Genetic Aptitude for Educational Attainment (GAEA) on risk for 10 psychiatric disorders divided into 4 groups: Internalizing, Externalizing, Eating/Compulsive and Psychotic. Educational attainment and psychiatric and substance use disorder information were obtained from national Swedish registries. GAEA and disorder-specific family genetic risk score (FGRS) were calculated from extended pedigrees. In males, information on IQ and resilience was obtained from the Swedish conscript registry. Affected individuals were born in Sweden from 1973–1995 to Swedish born parents. Controlling for disorder specific FGRS, GAEA were negatively and substantially associated with risk for externalizing and... (More)

We seek to clarify the impact of the Genetic Aptitude for Educational Attainment (GAEA) on risk for 10 psychiatric disorders divided into 4 groups: Internalizing, Externalizing, Eating/Compulsive and Psychotic. Educational attainment and psychiatric and substance use disorder information were obtained from national Swedish registries. GAEA and disorder-specific family genetic risk score (FGRS) were calculated from extended pedigrees. In males, information on IQ and resilience was obtained from the Swedish conscript registry. Affected individuals were born in Sweden from 1973–1995 to Swedish born parents. Controlling for disorder specific FGRS, GAEA were negatively and substantially associated with risk for externalizing and internalizing disorders, minimally associated with psychotic disorder risk and positively and modestly associated with risk for eating/compulsive disorders. While the majority of GAEA effect on risk for externalizing disorders was mediated through impact on IQ, for internalizing disorders, mediation was largely through resilience. For externalizing and internalizing disorders, interactions between GAEA and disorder specific FGRS were robust and negative – the slope of disorder risk with increasing genetic liability was steepest in those with low GAEA. For eating disorders, interactions were modest and positive –the slope of risk with increasing genetic liability being steepest in individuals with high GAEA. We found that the impact of GAEA on risk for psychiatric and substance can be substantial and varies widely across disorders in magnitude, direction, and mediation. GAEA also often interacts, sometimes robustly, with disorder specific genetic risk factors. Comprehensive risk models for psychiatric disorders should consider the inclusion of GAEA.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Psychiatry
volume
30
issue
7
pages
8 pages
publisher
Springer Nature
external identifiers
  • pmid:40247129
  • scopus:105002733955
ISSN
1359-4184
DOI
10.1038/s41380-025-03022-z
language
English
LU publication?
yes
id
b781b78d-3a15-4b9a-9318-242f3f99a31b
date added to LUP
2025-08-29 13:31:51
date last changed
2025-08-30 03:00:02
@article{b781b78d-3a15-4b9a-9318-242f3f99a31b,
  abstract     = {{<p>We seek to clarify the impact of the Genetic Aptitude for Educational Attainment (GAEA) on risk for 10 psychiatric disorders divided into 4 groups: Internalizing, Externalizing, Eating/Compulsive and Psychotic. Educational attainment and psychiatric and substance use disorder information were obtained from national Swedish registries. GAEA and disorder-specific family genetic risk score (FGRS) were calculated from extended pedigrees. In males, information on IQ and resilience was obtained from the Swedish conscript registry. Affected individuals were born in Sweden from 1973–1995 to Swedish born parents. Controlling for disorder specific FGRS, GAEA were negatively and substantially associated with risk for externalizing and internalizing disorders, minimally associated with psychotic disorder risk and positively and modestly associated with risk for eating/compulsive disorders. While the majority of GAEA effect on risk for externalizing disorders was mediated through impact on IQ, for internalizing disorders, mediation was largely through resilience. For externalizing and internalizing disorders, interactions between GAEA and disorder specific FGRS were robust and negative – the slope of disorder risk with increasing genetic liability was steepest in those with low GAEA. For eating disorders, interactions were modest and positive –the slope of risk with increasing genetic liability being steepest in individuals with high GAEA. We found that the impact of GAEA on risk for psychiatric and substance can be substantial and varies widely across disorders in magnitude, direction, and mediation. GAEA also often interacts, sometimes robustly, with disorder specific genetic risk factors. Comprehensive risk models for psychiatric disorders should consider the inclusion of GAEA.</p>}},
  author       = {{Kendler, Kenneth S. and Ohlsson, Henrik and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{1359-4184}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{3160--3167}},
  publisher    = {{Springer Nature}},
  series       = {{Molecular Psychiatry}},
  title        = {{The moderation of genetic risk for ten major psychiatric and substance use disorders by the genetic aptitude for educational attainment}},
  url          = {{http://dx.doi.org/10.1038/s41380-025-03022-z}},
  doi          = {{10.1038/s41380-025-03022-z}},
  volume       = {{30}},
  year         = {{2025}},
}