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Age at onset as an index of genetic heterogeneity in major psychiatric and substance use disorders

Kendler, Kenneth S. ; Henrik, Ohlsson LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2024) In Psychological Medicine 54(15). p.4335-4337
Abstract

Background Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS). Methods We examined, in individuals born in Sweden 1940-2003, whether AAO for five primary disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), and schizophrenia (SZ) - was associated with varying levels of GRRs with a range of informative secondary disorders and traits. Results Our disorders displayed a varying pattern of change of GRRs with increasing AAO. At one end was SZ, where all GRRs rose with increasing AAO meaning that... (More)

Background Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS). Methods We examined, in individuals born in Sweden 1940-2003, whether AAO for five primary disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), and schizophrenia (SZ) - was associated with varying levels of GRRs with a range of informative secondary disorders and traits. Results Our disorders displayed a varying pattern of change of GRRs with increasing AAO. At one end was SZ, where all GRRs rose with increasing AAO meaning that SZ became increasing genetically heterogeneous with later AAO. The most balanced disorder was AUD where, with increasing AAO, GRRs rose for AD, BD, and MD and declined for DUD, CB, and ADHD. That is, at young AAO, AUD had high levels of genetic risk for other externalizing disorders while at older AAO, high genetic risk for internalizing disorders were more prominent. MD was at the continuum's other end where all GRRs, except for AD, decreased with higher AAO, meaning that MD became increasingly genetically homogeneous with later AAO. Conclusions Genetic heterogeneity was robustly associated with AAO across our five primary disorders with substantial inter-disorder differences in the observed patterns. In particular, young AAO was associated with maximal genetic homogeneity for SZ and DUD while older AAO had greater genetic homogeneity for MD with AUD falling in between.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
age at onset, depression, drug use disorder, genetic heterogeneity, genetic risk, schizophrenia
in
Psychological Medicine
volume
54
issue
15
pages
3 pages
publisher
Cambridge University Press
external identifiers
  • scopus:85210900048
  • pmid:39618328
ISSN
0033-2917
DOI
10.1017/S0033291724002630
language
English
LU publication?
yes
id
7b883e62-d57c-4ffc-b63f-27d39f7b2f94
date added to LUP
2025-01-31 15:33:59
date last changed
2025-07-05 04:21:39
@article{7b883e62-d57c-4ffc-b63f-27d39f7b2f94,
  abstract     = {{<p>Background Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS). Methods We examined, in individuals born in Sweden 1940-2003, whether AAO for five primary disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), and schizophrenia (SZ) - was associated with varying levels of GRRs with a range of informative secondary disorders and traits. Results Our disorders displayed a varying pattern of change of GRRs with increasing AAO. At one end was SZ, where all GRRs rose with increasing AAO meaning that SZ became increasing genetically heterogeneous with later AAO. The most balanced disorder was AUD where, with increasing AAO, GRRs rose for AD, BD, and MD and declined for DUD, CB, and ADHD. That is, at young AAO, AUD had high levels of genetic risk for other externalizing disorders while at older AAO, high genetic risk for internalizing disorders were more prominent. MD was at the continuum's other end where all GRRs, except for AD, decreased with higher AAO, meaning that MD became increasingly genetically homogeneous with later AAO. Conclusions Genetic heterogeneity was robustly associated with AAO across our five primary disorders with substantial inter-disorder differences in the observed patterns. In particular, young AAO was associated with maximal genetic homogeneity for SZ and DUD while older AAO had greater genetic homogeneity for MD with AUD falling in between.</p>}},
  author       = {{Kendler, Kenneth S. and Henrik, Ohlsson and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{0033-2917}},
  keywords     = {{age at onset; depression; drug use disorder; genetic heterogeneity; genetic risk; schizophrenia}},
  language     = {{eng}},
  number       = {{15}},
  pages        = {{4335--4337}},
  publisher    = {{Cambridge University Press}},
  series       = {{Psychological Medicine}},
  title        = {{Age at onset as an index of genetic heterogeneity in major psychiatric and substance use disorders}},
  url          = {{http://dx.doi.org/10.1017/S0033291724002630}},
  doi          = {{10.1017/S0033291724002630}},
  volume       = {{54}},
  year         = {{2024}},
}