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This article provides an introduction to the role of microRNAs in the nervous system and outlines their potential involvement in the pathophysiology of schizophrenia, which is hypothesized to arise owing to environmental factors and genetic predisposition.
Genome-wide association studies have identified common genetic variants shared among patients with schizophrenia.1 Most of the significantly associated single-nucleotide polymorphisms were found in noncoding DNA regions, where they could alter transcription factor binding sites or the activity of gene promoters or influence transcript splicing. Several single-nucleotide polymorphisms were in close approximation to the gene loci of microRNAs, suggesting that these variants could influence microRNA expression levels. While such alterations may be subtle and not necessarily directly pathogenic, it is known that microRNAs also respond to environmental factors such as prenatal stress.2 Such factors trigger changes in DNA methylation or histone modifications and alter access of transcription factors to the DNA, leading to varying levels of transcripted microRNAs. Thus, if the endogenous microRNA levels are already altered owing to even minor sequence variations in the microRNA gene locus, this could result in an atypical response to environmental stimuli, resulting in disease-associated changes at the molecular and cellular levels.
Tsai L, Siegert S. How MicroRNAs Are Involved in Splitting the Mind. JAMA Psychiatry. 2016;73(4):409–410. doi:10.1001/jamapsychiatry.2015.3144
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