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

AI Article Synopsis

  • The study investigates the relationship between age at onset (AAO) of psychiatric disorders and genetic heterogeneity using Family Genetic Risk Scores (FGRS).
  • Researchers focused on five disorders: drug use disorder, alcohol use disorder, major depression, bipolar disorder, and schizophrenia, analyzing individuals born in Sweden between 1940-2003.
  • Results showed that as AAO increased, schizophrenia displayed increased genetic risk, while major depression became more genetically homogenous, highlighting significant inter-disorder differences in how AAO affects genetic risks.

Article 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 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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Source
http://dx.doi.org/10.1017/S0033291724002630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650156PMC

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