A new research study has revealed a correlation between schizophrenia and somatic copy-number variants—genetic mutations that occur post-inheritance. This marks one of the initial studies to demonstrate a link between somatic mutations and schizophrenia risk.
A study in Cell Genomics has found a link between somatic genetic mutations and schizophrenia. Researchers analyzed over 20,000 blood samples, identifying genes NRXN1 and ABCB11 as associated with schizophrenia when disrupted during fetal development. The finding highlights the role of non-inherited genetic mutations in psychiatric disorders, and the team plans to explore other potential associated mutations.
As a psychiatric disorder with onset in adulthood, schizophrenia is thought to be triggered by some combination of environmental factors and genetics, although the exact cause is still not fully understood. In a study published in the journal Cell Genomics on July 6, researchers find a correlation between schizophrenia and somatic copy-number variants, a type of mutation that occurs early in development but after genetic material is inherited. This study is one of the first to rigorously describe the relationship between somatic—not inherited—genetic mutations and schizophrenia risk.
“We originally thought of genetics as the study of inheritance. But now we know that genetic mechanisms go way beyond that,” says senior author Chris Walsh, an investigator at the Howard Hughes Medical Institute and chief of genetics and genomics at Boston Children’s Hospital. “We’re looking at mutations that are not inherited from the parents.”
The researchers analyzed genotype-marker data from over 20,000 blood samples of people with or without schizophrenia from the Psychiatric Genomics Consortium. They ultimately identified two genes—NRXN1 and ABCB11—that correlated with schizophrenia cases when disrupted in utero. NRXN1, a gene that helps transmit signals throughout the brain, has been associated with schizophrenia before. However, this is the first study to associate somatic, not inherited, NRXN1 mutations with schizophrenia.
Schizophrenia-associated somatic copy number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions. Credit: Cell Genomics / Maury et al.
Unlike inherited mutations, which are present in all the cells of the body, somatic mutations are only present in a fraction of cells based on when and where a mutation occurred. If a mutation occurs early in development, it is expected that the variant is present throughout the body in a mosaic pattern. On the basis of this principle, researchers can identify somatic mutations that occurred early in development and are present not only in the brain but also in a fraction of cells in the blood.
“If a mutation occurs after fertilization when there are only two cells, the mutation will be present in half of the cells of the body,” says Walsh. “If it occurs in one of the first four cells, it will be present in about a quarter of the cells of the body, and so on.”
The second gene the researchers identified, ABCB11, is most known to encode a liver protein. “That one came out of nowhere for us,” says Eduardo Maury, a student in Harvard-<span class=”glossaryLink” aria-describedby=”tt” data-cmtooltip=”
MIT
MIT is an acronym for the Massachusetts Institute of Technology. It is a prestigious private research university in Cambridge, Massachusetts that was founded in 1861. It is organized into five Schools: architecture and planning; engineering; humanities, arts, and social sciences; management; and science. MIT’s impact includes many scientific breakthroughs and technological advances. Their stated goal is to make a better world through education, research, and innovation.
” data-gt-translate-attributes=”[“attribute”:”data-cmtooltip”, “format”:”html”]”>MIT’s MD-PhD program. “There have been some studies associating mutations in this gene with treatment-resistant schizophrenia, but it hasn’t been strongly implicated in schizophrenia per se.”
When the team investigated further, they found that ABCB11 is also expressed in very specific subsets of neurons that carry dopamine from the brainstem to the cerebral cortex. Most schizophrenia drugs are thought to act on these cells to decrease an individual’s dopamine levels, so this might explain why the gene is associated with treatment resistance.
Next, the team is working towards identifying other acquired mutations that might be associated with schizophrenia. Given that the study analyzed blood samples, it will be important to look at more brain-specific mutations that might have been too subtle or recent in a patient’s life for this analysis to detect. In addition, somatic deletions or duplications might be an under-investigated risk factor associated with other disorders.
“With this study, we show that it is possible to find somatic variants in a psychiatric disorder that develops in adulthood,” says Maury. “This opens up questions about what other disorders might be regulated by these kinds of mutations.”
Reference: “Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions” by Eduardo A. Maury, Maxwell A. Sherman, Giulio Genovese, Thomas G. Gilgenast, Tushar Kamath, S.J. Burris, Prashanth Rajarajan, Erin Flaherty, Schahram Akbarian, Andrew Chess, Steven A. McCarroll, Po-Ru Loh, Jennifer E. Phillips-Cremins, Kristen J. Brennand, Evan Z. Macosko, James T.R. Walters, Michael O’Donovan, Patrick Sullivan and Psychiatric Genomic Consortium Schizophrenia and CNV workgroup, 6 July 2023, Cell Genomics. DOI: 10.1016/j.xgen.2023.100356
This work was supported by the Harvard/MIT MD-PhD program, the Biomedical Informatics and Data Science Training Program, the Ruth L. Kirschstein NRSA F31 Fellowship, the <span class=”glossaryLink” aria-describedby=”tt” data-cmtooltip=”
National Institutes of Health
The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.
” data-gt-translate-attributes=”[“attribute”:”data-cmtooltip”, “format”:”html”]”>National Institutes of Health, the Stanley Center for Psychiatric Research, the Brain Somatic Mosaicism Network, the Psychiatric Genomics Consortium, the Allen Discovery Center for Human Brain Evolution, the Howard Hughes Medical Institute, the Suh Kyungbae Foundation, and the Chan Zuckerberg Initiative and Scientific Interfaces. The authors declare no conflicts of interest.
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.
Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.
Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.
Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.
The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.
“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.
Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.
Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.
Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.
A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.
This report by The Canadian Press was first published Sept. 10, 2024.
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