Evolutionarily recent retrotransposons contribute to schizophrenia.

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.