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The mass marketing of genetic testing kits, such as Helix and 23andMe, suggests that our DNA can provide simple answers about our health. In reality, applying genetic knowledge to improve a patient’s health is much more complex.
For more than 20 years, CAMH has been at the forefront of bringing genetic testing from lab to clinic, to identify which medications are most likely to work for a given patient without side-effects. Physicians can use the results to select medications or adjust doses. Patients are spared trying one medication after another. “We have shown that we can create a practical, affordable and simple report that works,” says Dr. Daniel Mueller.
Through the IMPACT study, led by Dr. James Kennedy, thousands of patients across Ontario have had genetic testing. The GeneSight test panel analyzes eight genes to provide information on 33 psychiatric drugs. It was developed by Assurex Health, which has a partnership with CAMH. For depression and anxiety, the test has been shown to reduce the severity of patients’ symptoms.
While the field seems to be approaching a tipping point—with pharmacies now selling genetic tests directly to customers—researchers caution that there is still
a lot to learn.
At CAMH, powerful computing techniques such as machine learning are being used to validate and identify new genetic markers. There is potential to develop multi-gene risk scores to predict medication responses based on hundreds or even thousands of genes, which Dr. Mueller’s team is also applying to unravel the genetic underpinnings of aging and depression onset. Dr. Rachel Tyndale is expanding her research on gene-guided treatment for nicotine addiction into diverse populations that may metabolize drugs differently, such as Indigenous peoples and pregnant women. And the IMPACT study continues to build evidence to show that genetic testing is effective for patients, and more efficient and less costly for the health care system.
A timeline of CAMH impacts on genetic testing for medication response
The role of genes in smoking
A 1998 CAMH study in Nature shows that smokers with a certain genetic marker (CYP2A6) are less likely to develop a nicotine addiction and will smoke fewer cigarettes. Ongoing research shows that the same genetic marker can be used to predict the best treatment for nicotine addiction.
The first Canadian clinic
CAMH opens Canada’s first pharmacogenetics research clinic for mental illness in 2008. The clinic is dedicated to understanding how patients’genes influence their bodies’ response to medications for depression, anxiety, schizophrenia and other illnesses.
Tackling serious side-effects
A series of studies from 2010 to 2015 identifies six genes that predict who is at higher risk of one of the most serious side-effects of antipsychotic medications—weight gain.
Based on these findings, an innovative treatment algorithm is developed and is being tested at CAMH and through an international consortium.
Into the community
Through the Tanenbaum Centre for Pharmacogenetics, CAMH begins the large-scale IMPACT study in 2012 to assess genetic testing in everyday clinical care, through family physicians and psychiatrists across Ontario and beyond.
Evidence for nicotine addiction
A 2015 Lancet study shows that gene testing is effective in guiding treatment for nicotine addiction. The genetic marker CYP2A6 can be used to indicate whether a nicotine patch or the medication varenicline should be used.
Individual to international impact
More than 11,200 people, referred by more than 3,000 physicians, have had genetic testing through CAMH to guide medication prescribing.
In a 2018 study, use of the GeneSight test panel improves symptoms of depression, and 15 per cent of patients go into remission.
Centres from around the world seek CAMH’s guidance on implementing genetic testing in clinical care.
The future: The power of big data
Applying advanced computing techniques, such as machine learning, holds the potential to accelerate discovery.
The development of polygenic risk scores, with results based on thousands of genes, may improve predictions. A risk score to optimize smoking treatment is the first to be developed.
After decades of research, the uptake of genetic testing accelerates
Toronto origins of pharmacogenetics
The University of Toronto’s Werner Kalow, a pioneer in the field of pharmacogenetics, shows in 1957 that genes are causing an anesthetic drug to be fatal for some patients. Five years later, he publishes the field’s first textbook, “Pharmacogenetics: Heredity and Response to Drugs."
In 2005, the U.S. Food and Drug Administration (FDA) clears the use of testing with two genetic markers (CYP2D6 and CYP2C19), but this is not widely translated into clinical care.
Canadian pharmacies now sell genetic tests directly to customers, without physician referrals.
The FDA authorizes the first direct-to-consumer commercial test by 23andMe in 2018—but states that results must not be used to make any medical decisions, and must first be confirmed through independent genetic testing.
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