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Evolutionarily recent retrotransposons contribute to schizophrenia.

Giorgia Modenini1, Paolo Abondio1,2, Guia Guffanti3

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Polymorphic transposable elements (TEs) in the human genome may influence schizophrenia risk. This study identified 38 non-reference TEs (nrTEs) potentially linked to schizophrenia, with 9 affecting gene expression in the brain.

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Area of Science:

  • Genomics
  • Neuroscience
  • Molecular Biology

Background:

  • Transposable elements (TEs) comprise a significant portion of the human genome.
  • Polymorphic non-reference TEs (nrTEs) are increasingly implicated in complex diseases.
  • A cis-regulatory role for nrTEs in cognitive disorders like schizophrenia has been proposed.

Purpose of the Study:

  • To identify specific polymorphic nrTEs associated with an increased risk of schizophrenia.
  • To investigate the functional impact of these nrTEs on brain gene regulation.

Main Methods:

  • Genome-wide inspection of nrTE content in dorsolateral prefrontal cortex samples from individuals with schizophrenia and controls.
  • Haplotype-based methods for confirmation of candidate nrTEs.
  • In silico functional analysis to assess regulatory roles (eQTLs/sQTLs).

Main Results:

  • Identified 38 nrTEs potentially contributing to schizophrenia risk.
  • Confirmed two of these nrTEs using haplotype-based approaches.
  • Found that 9 of the 38 nrTEs function as expression/alternative splicing quantitative trait loci (eQTLs/sQTLs) in the brain.

Conclusions:

  • This study presents the first identification of polymorphic nrTEs potentially influencing brain function.
  • Evolutionarily young nrTEs may play a crucial role in the neurodevelopmental and ethiopathogenesis of schizophrenia.
  • These findings suggest a novel genetic mechanism contributing to this complex psychiatric disorder.