Epigenetic and Genetic Connections to Schizophrenia in the Developing Brain

Researchers investigate DNA methylation quantitative trait loci and neurodevelopment

DNA methylation and Schizophrenia

Connections between epigenetics and schizophrenia have been previously speculated, although no one knows for certain exactly how epigenetic tags may or may not control the development of the disease. Now, research conducted by a group of international scientists is helping us to understand the epigenetic and genetic components of schizophrenia in the developing human brain.

Headed by researchers from the University of Exeter Medical School, Cardiff University and King’s College London, the study was published in Nature Neuroscience and details, for the first time, the role genetic variation plays on DNA methylation in the developing brain. This epigenetic mechanism is known to have significant impact on the expression of genes and their function. Understanding the data could help refine our comprehension of the genetic indicators that are linked to various diseases, particularly those involving neurodevelopment.

DNA methylation is a well-known epigenetic chemical modification that occurs to the genetic sequence that makes up our DNA. These chemical tags can impact where and when genes are expressed. It is thought to be influenced by various factors experienced throughout a lifetime as well as modifiable by the genetic code. This is one potential pathway between the variation of genes and disease. Previously, genetic alterations have been shown to adjust the expression of genes at certain times of development.

The researchers discovered that schizophrenia-related genetic variants were enriched for changes that influence DNA methylation in the fetal brain. Certain genetic risk factors for schizophrenia are linked to changes in DNA methylation very early in one’s life, even as soon as the first and second trimesters.

The researchers reported that fetal brain DNA methylation quantitative trait loci were “enriched amongst risk loci identified in a recent large-scale genome-wide association study (GWAS) of schizophrenia.” They showed that most fetal brain DNA methylation quantitative trait loci were developmentally stable, although some were characterized by fetal-specific effects. They also demonstrated how DNA methylation quantitative trait loci “can be used to refine GWAS loci through the identification of discrete sites of variable fetal brain methylation associated with schizophrenia risk variants.”

Dr. Ellis Hannon, from the University of Exeter Medical School, said, “This data has particular relevance for disorders such as schizophrenia, where it is thought that changes early in brain development increase an individual’s liability to develop the illness later on in life. Therefore, understanding the genetic effects of risk variants on gene regulation during the earliest stages of brain development may point us towards the underlying biology of schizophrenia.”

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From the University of Exeter Medical School, Professor Jonathan Mill explained that the study builds on the significant progress recent research has made in identifying the genetic risks for schizophrenia.

Additionally, the researchers have made the data available to the research community online which could help facilitate understanding the results of future studies that investigate neurodevelopmental disorders and their potential epigenetic and genetic origins.

 

Source: Hannon, E., Spiers, H., Viana, J., Pidsley, R., Burrage, J., Murphy, T.M., Troakes, C., Turecki, G., O’Donovan, M.C., Schalkwyk, L.C., Bray, N.J., Mill, J. (2015). Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nature Neuroscience, Advance online publication.

Reference: University of Exeter. Schizophrenia-associated genetic variants affect gene regulation in the developing brain. 30 Nov 2015. Web.

About Bailey Kirkpatrick 123 Articles
Bailey Kirkpatrick is a science writer with a background in epigenetics and psychology and a passion for conveying scientific concepts to the wider community. She enjoys speculating about the implications of epigenetics and how it might impact our perception of wellbeing and the development of novel preventative strategies. When she’s not combing through research articles, she also enjoys discovering new foods, taking nighttime strolls, and discussing current events over a hoppy IPA or cold-brewed coffee.
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