Scientists identify genes that dramatically increase the risk of schizophrenia

Second study Together, they identify hundreds of common genetic mutations that contribute only to a small extent to schizophrenia, but together point to poor communication between brain cells as the main cause of the disorder.

By learning about the genes involved in schizophrenia, Dr. Joshua Gordon, director of the National Center of Neurology and Psychiatry, who partially funded the study, helped biologists study what’s wrong with the brain. Said that you can find a way to fix it. “They give us potential targets for treatment. That’s a big step forward here,” he said.

The researchers involved in the study emphasize that there is a long way to go before new drugs become available. However, the results open a “new study” on the causes of the disorder, said Benjamin Neale, director of genetics at the Stanley Psychiatric Research Center at the Broad Institute, who was involved in both studies. “It gives us new things to work on.”

It is well known that the majority of the risk of developing schizophrenia is due to genes, but it is difficult to pinpoint the details of which genes are involved and how they contribute to schizophrenia. .. “The situation is less ambiguous,” said Kristen Brenand, a professor of psychiatry and genetics at Yale School of Medicine.

Extensive studies compared the genomes of about 24,000 and 97,000 people with schizophrenia The person who was not in a state. Researchers have discovered rare mutations in 10 genes that dramatically increase the likelihood of developing schizophrenia.

“The risk of these mutations is very high,” said Tarzindersin, lead analyst at Broad Research and psychiatric geneticist at the institute. Some genes have helped test existing hypotheses about the causes of schizophrenia, but many of them have come as a complete surprise. “I don’t know what many of these genes are doing, and it’s very difficult,” he added.

The second study was conducted by the Psychiatry Genomics Consortium, an international team of hundreds of geneticists, psychiatrists, and data scientists. In 2014, the group identified 108 spots Along the human genome, there seems to be a difference between people with and without schizophrenia. Their new study compares the DNA of more than 76,000 people with schizophrenia with the DNA of 243,000 asymptomatic people and records the aggregation of genetic variation in up to 287 people.

Some of the genes in the study are important for the communication between brain cells that occurs at junctions called synapses. Director of the MRC Center for Consortium Research and Neuropsychiatric Genetics and Genomics at Cardiff University, Wales.

Especially the receiving side of synapses is often faulty People in distress schizophrenia. “It wasn’t particularly relevant in the past, and it of course gives you clues as to where to direct your treatment,” he said.

There are cures for schizophrenia, but they are only partial and not for everyone. These drugs primarily block the activity of a synaptic molecule called dopamine.

Neuroscientists have long hypothesized that another molecule at the synapse, called glutamate, plays a more fundamental role in the disorder. Genetic studies suggest that multiple genes associated with glutamate are important for schizophrenia, adding new urgency to the theory.

More importantly, insights related to more general people by studying rare mutations in which some of the same genes appear in both studies and may be highly effective and easy to understand. Mutations that suggest that it may lead to treatment. “It gives you not only hope, but real evidence that there is duplication in the mechanism,” Gordon said.

Dr. Joshua Loffman, a psychiatrist and neuroscientist at Massachusetts General Hospital Working on rare mutations is optimistic that it will lead to new drugs. He states that rare genetic mutations that increase the risk of heart attack helped scientists identify drug discovery targets that led to the development of cholesterol-lowering statins decades ago.

“It’s the model we’re aiming for in psychiatric genetics,” he said. “Although only a few people may be affected by a particular mutation, an manageable biological pathway that can be used to understand what is happening in the brain and develop better treatments. To identify. “

Scientists are already working on the creation of animals such as engineered human cells and mice with these mutations associated with schizophrenia. The goal is to understand exactly how these mutations affect brain cells and find drugs that can prevent, stop, or reverse damage.

Conrad Jegbe, a computational biologist at Mount Sinai School of Medicine, said the study provides “unprecedented insights” into the genes and brain cells involved in schizophrenia, but “it’s still incomplete information.” Is. “

He said the studies still explain only a small part of the total genetic contribution to schizophrenia, and that larger and more diverse studies will be needed to fill the gap. Part of the problem is that these genetic studies often rely primarily on data from Caucasians. The new study was more diverse than the previous study, but blacks and Hispanics still accounted for a relatively small proportion of participants.

“If these studies can expand population diversity, we can expand the catalog of disease-causing mutations,” says Iyegbe.

One day, when these genes are further cataloged, doctors may be able to predict the risk of developing schizophrenia simply by examining the genes. So far, scientists say that the greatest risk factor genes are too rare to justify the test, and common mutations pose too little risk to make meaningful predictions. Is called.

“We are on the road to getting to know enough about genetics to take some clinical trials,” Loffman said. “Therefore, we are optimistic that this kind of research will be very influential in the long run.”

Shin hopes that new genetic clues will ultimately “open the way to new therapies” that are more effective and have fewer side effects, but from the final word on the genetics of schizophrenia. It also states that it is far from it. “This is still in the early stages of gene discovery. There are the first 10 genes, and hundreds.”

Ryan Cross can be reached at [email protected].. Follow him on Twitter @RLCscienceboss..