A trailblazing global scientific collaboration has identified more than 100 spots in human DNA that appear to contribute to the risk of developing schizophrenia, vastly expanding the understanding of the complex genetics behind the disease.
Prof. Jo Knight, a senior scientist at the Centre for Addiction and Mental Health in Toronto, collaborated on the biggest-ever psychiatric genetics study. (CAMH/Canadian Press)
Scientists from more than 30 countries published the findings in the journal Nature on Tuesday, revealing 83 previously unknown genetic markers for the psychiatric condition.
"It's the biggest by far in terms of any psychiatric genetic study," said Prof. Jo Knight, a behavioural neuroscientist at the Centre for Addiction and Mental Health in Toronto and a contributor to the research.
"This really is the beginning of a group of many, many studies that will produce lots more information about the disease as people drill down into very specific hypotheses and try to test interactions with the environment, or gene-to-gene interactions."
Knight said having any one of the genetic markers for schizophrenia would give someone a "very small" risk of developing the disease, but "the more that you have, the more likely you are." However, since environmental factors still play an important role, such all-out prediction "is still incredibly poor," she said.
"We're not anywhere close to the point where you might say this individual will go on to develop schizophrenia. You couldn't test children with this data and predict an outcome at this point."
150,000 subjects
More than 100 researchers from around the world collaborated in the effort. The study included genetic information from more than 150,000 people — nearly 37,000 of them diagnosed with schizophrenia. Researchers found 108 genetic markers that increase the risk of getting the disease, and scientists say there are still likely more to be found.
Schizophrenia is a debilitating mental disorder often emerging in the teens and early 20s that makes it hard to tell the difference between what is real and not real, and affects about one per cent of the population. The price tag of health care, social costs and lost productivity is estimated at $6.85 billion a year in Canada alone.
The new findings implicate genes expressed in brain tissue, particularly those related to the functioning of neurons and the pathways that enable chemical and electrical signalling between these brain cells, known as synapses.
They also give weight to a theory that genes active in immune-system functioning may also be involved with schizophrenia, suggesting that it could be an autoimmune disease, at least in part.
Scientists had already known that families with autoimmune disorders tend to have higher rates of schizophrenia, and there's been a link between certain viral infections in the second trimester of pregnancy and higher rates of schizophrenia in offspring.
The results are a "big step" toward finding drug therapies, said study lead author Dr. Michael O'Donovan, deputy director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine in Wales. While 108 genetic markers are a lot, the study authors say they tend to implicate a narrower group of biological functions, giving some but not too many hints for scientists to pursue.
Affirms existing theories
Another Canadian contributor to the study said the results show current drug treatments for schizophrenia aren't totally off-base. Prof. Jim Kennedy, Knight's colleague at the Centre for Addiction and Mental Health in Toronto, said one of the newly discovered genetic markers for schizophrenia is in an area of DNA that helps code for the brain's dopamine receptors.
"It does provide a kind of independent stamp of approval that the drugs we're approving are not misguided, all these drugs for schizophrenia that bind to these dopamine D2 receptors," Kennedy said — though he acknowledged that the medications are still "by no means ideal" and have many side effects.
Kennedy said other genetic markers uncovered by the new research are involved in the neurotransmitter glutamate, which lends credence to research trying to find a link between glutamate irregularities and schizophrenia.
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