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A new study, published in Science, has unveiled detailed information regarding genetic variation in brain cells, which could potentially lead to targeted treatments for diseases like schizophrenia and Alzheimer’s. The study was conducted by the PsychENCODE collaboration, established by the National Institutes of Health in 2015. Previous research has shown a strong connection between genetics and neuropsychiatric diseases, with a higher heritability for brain-related conditions compared to cancer or heart disease. The goal of the study was to understand how genetic variation contributes to these diseases at a mechanistic level.

Researchers analyzed over 2.8 million brain cells from 388 individuals, including those with neuropsychiatric disorders such as schizophrenia, bipolar disorder, and Alzheimer’s, as well as healthy subjects. They identified 28 different cell types and examined gene expression and regulation within those cells. By linking gene expression to regulatory regions, researchers were able to understand the effect of gene variants in the brain at a cellular level. The study revealed that genes associated with neurotransmitters showed higher variability across cell types compared to individuals, indicating more targeted drug treatments.

Using the data generated from the analysis, researchers constructed genetic regulatory networks within cells and communication networks between cells, which were then utilized in a machine learning model. This model could predict whether an individual had a brain disease based on their genetic information. By examining the network components that contributed to these predictions, researchers were able to identify specific genes and cell types that could be potential drug targets. For example, the model accurately predicted bipolar disorder based on two genes in three cell types and identified six genes in six cell types contributing to a schizophrenia prediction.

The model could also simulate genetic perturbations to predict how they might impact the network and an individual’s health, which could be valuable for drug design and testing. By leveraging these findings, precision medicine approaches for neuropsychiatric diseases could be advanced, offering targeted treatments based on an individual’s genetic profile. The consortium behind the study has made their results and model available to other researchers, enabling further exploration and discovery in the field. This initiative aims to assist researchers in better understanding the genetic mechanisms underlying brain diseases and identifying potential drug targets for further investigation.

Overall, the study presents a significant step towards personalized and targeted treatments for neuropsychiatric diseases by unraveling the genetic variation in brain cells. By delving into the intricate genetic landscape of the brain, researchers can gain insight into disease mechanisms and identify potential drug targets. The availability of the study’s data and model to other researchers fosters collaboration and innovation in the field of neuropsychiatric research. Ultimately, these findings hold promise for the development of precision medicines tailored to individual genetic profiles, offering hope for more effective treatments for diseases like schizophrenia and Alzheimer’s.

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