Tracking the cellular and genetic roots of neuropsychiatric disease
A new study of nearly 400 human brains links genetic variants to genes and cell types, which could help enable precision-medicine for neuropsychiatric disease.A new analysis has revealed detailed information about genetic variation in brain cells that could open new avenues for the targeted treatment of diseases such as schizophrenia and Alzheimer’s disease.
A new analysis has revealed detailed information about genetic variation in brain cells that could open new avenues for the targeted treatment of diseases such as schizophrenia and Alzheimer’s disease. The findings, reported May 23 in Science, were the result of a multi-institutional collaboration known as PsychENCODE, founded in 2015 by the National Institutes of Health, which seeks new understandings of genomic influences on neuropsychiatric disease. The study was published alongside related studies in Science, Science Advances, and Science Translational Medicine.
The study included data from 388 people, including healthy individuals and some with brain-related diseases and disorders. More than 2.8 million brain cells across 28 different cell types were analyzed. The researchers used their findings to construct genetic regulatory and cellular communication networks, and a machine learning model built off of those networks was able to predict disease diagnosis from an individual’s genetic information.
Previous research has established a strong link between a person’s genetics and their likelihood of developing neuropsychiatric disease, says Mark Gerstein, the Albert L. Williams Professor of Biomedical Informatics at Yale School of Medicine and senior author of the new study.
“The correlations between genetics and your susceptibility to disease are much higher for brain diseases than for cancer or heart disease,” said Gerstein. “If your parents have schizophrenia, you’re much more likely to get it than you are to get heart disease if your parents have the disease. There is a very large heritability for these brain-related conditions.”
That’s useful because if you have a variant of interest, you can now link it to a gene,” said Gerstein. “And that’s really powerful because it helps you interpret the variants. It helps you understand what effect they’re having in the brain. And because we looked across cell types, our data also allow you to connect that variant to an individual cell type of action.”
The researchers also assessed how particular genes, such as those associated with neurotransmitters, varied across individuals and cell types, finding variability was usually higher across cell types than across individuals. This pattern was even stronger for genes that code for proteins targeted for drug treatment.
“And that’s generally good for a drug,” Gerstein said. “It means that those drugs are homing in on particular cell types and not affecting your whole brain or body. It also means those drugs are more likely to be unaffected by genetic variants and work in many people.”
A new analysis has revealed detailed information about genetic variation in brain cells that could open new avenues for the targeted treatment of diseases such as schizophrenia and Alzheimer’s disease. The findings, reported May 23 in Science, were the result of a multi-institutional collaboration known as PsychENCODE, founded in 2015 by the National Institutes of Health, which seeks new understandings of genomic influences on neuropsychiatric disease. The study was published alongside related studies in Science, Science Advances, and Science Translational Medicine.
Previous research has established a strong link between a person’s genetics and their likelihood of developing neuropsychiatric disease, says Mark Gerstein, the Albert L. Williams Professor of Biomedical Informatics at Yale School of Medicine and senior author of the new study.
“The correlations between genetics and your susceptibility to disease are much higher for brain diseases than for cancer or heart disease,” said Gerstein. “If your parents have schizophrenia, you’re much more likely to get it than you are to get heart disease if your parents have the disease. There is a very large heritability for these brain-related conditions.”
The researchers also assessed how particular genes, such as those associated with neurotransmitters, varied across individuals and cell types, finding variability was usually higher across cell types than across individuals. This pattern was even stronger for genes that code for proteins targeted for drug treatment.
“And that’s generally good for a drug,” Gerstein said. “It means that those drugs are homing in on particular cell types and not affecting your whole brain or body. It also means those drugs are more likely to be unaffected by genetic variants and work in many people.”
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