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Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
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Schizophrenia risk-associated SNPs affect expression of microRNA 137 host gene: a postmortem study.

Ningping Feng1, Ajeet Mandal1, Ananya Jambhale1

  • 1Human Brain Collection Core, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, 10 Center Drive, Bldg 10, room 4N218, Bethesda, MD 20892, United States.

Human Molecular Genetics
|September 6, 2024
PubMed
Summary

Schizophrenia risk variants in MIR137HG are linked to altered expression of its immature transcripts, suggesting a role in genetic predisposition. Further validation is needed to confirm these findings in brain tissue.

Keywords:
MIR137eQTLlong-non-coding RNApostmortemschizophrenia

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Area of Science:

  • Neurogenetics
  • Molecular Psychiatry

Background:

  • Common variants in MIR137HG and DPYD are associated with schizophrenia risk, confirmed by the Psychiatric Genomics Consortium (PGC).
  • Understanding the functional impact of these risk-associated single nucleotide polymorphisms (SNPs) is crucial for elucidating schizophrenia pathogenesis.

Purpose of the Study:

  • To investigate the association between schizophrenia risk-associated SNPs in the MIR137HG genomic region and the expression of miR-137 host gene transcripts.
  • To examine MIR137HG transcript expression in postmortem brain samples from individuals with schizophrenia and controls.

Main Methods:

  • Quantitative PCR (qPCR) and RNA-sequencing (RNA-Seq) were used to analyze mature and immature MIR137HG transcripts.
  • Expression levels were studied in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of schizophrenia patients and controls.

Main Results:

  • No differential expression of mature miR-137, MIR137HG, or its transcripts was observed between schizophrenia cases and controls.
  • Two PGC-identified schizophrenia risk SNPs, rs11165917 and rs4274102, were associated with MIR137HG-203 long non-coding RNA transcript expression in European ancestry individuals.
  • Carriers of the risk allele for rs11165917 showed significantly lower MIR137HG-203 expression, though this was not validated by short-read sequencing.

Conclusions:

  • The study did not find differential expression of mature MIR137HG transcripts in schizophrenia.
  • Schizophrenia risk SNPs may influence the expression of immature MIR137HG transcripts, potentially contributing to genetic risk.
  • Further research is required to validate the role of immature MIR137HG transcripts in schizophrenia.