The Silent Genomes Project is working to ensure Indigenous genomes are included as reference data, an important early step when diagnosing rare genetic conditions.
By Mark Sampson
Having a child with a suspected rare, genetic condition can be one of the most harrowing experiences a parent can go through. The fear and uncertainty, the concerns over treatments and their efficacy, and worries about what such a diagnosis might mean for other members of one’s family can all be overwhelming. One of the few saving graces may come from the knowledge that the science of genetics has advanced to the point where we can now diagnose, treat and manage many diseases in ways we couldn’t decades ago.
According to GWAS Diversity Monitor, 95 percent of all genome studies are based on people of European ancestry, which leads to gaps – or whole chasms – in data involving other ethnicities and the diseases to which they are more susceptible. Indeed, less than 1 percent of all studies are based on Indigenous people, and this has huge implications here in Canada for First Nations, Métis, and Inuit communities. This matters because Indigenous genomic reference data, needed for accurate diagnosis, is not represented in commonly used public databases built through research. While leading-edge genomic technologies are becoming routinely available to other Canadians, Indigenous people often have little or no access to these technologies, increasing the health disparity gap.
The Silent Genomes Project is a game-changing effort to address this inequity, by bringing life-changing genomic diagnosis to children and families while ensuring Indigenous-led governance over biological samples and health data, says Project Leader, Dr. Laura Arbour.
The Silent Genomes Project Leader and a professor of Medical Genetics at the University of British Columbia (UBC), a researcher and physician specializing in Clinical Genetics
Dr. Arbour, a professor of Medical Genetics at the University of British Columbia (UBC), a researcher and physician specializing in Clinical Genetics, says the origin of this genetic divide should not come as any surprise. She points to the long history of mistrust that many Indigenous communities have felt not only toward physicians and other health care professionals, but toward medical researchers as well.
“This is happening for all the reasons we keep hearing about,” Dr. Arbour says. “Trust is a huge issue and there are systemic reasons why Indigenous people would be mistrustful of not only research, but clinical care in general.”
The Silent Genomes Project is establishing processes with Indigenous partners for safe governance of genomic data. It is also making it a priority to address barriers to accessing genetic/genomic health care. This work is culminating with the development of an Indigenous Background Variant Library (IBVL) and improved diagnosis for Indigenous patients. One of the core tenets of the Silent Genomes Project centres around the use of biological samples: it considers the DNA to be “on loan” from the community to the researcher for the purpose of the research for which consent was obtained. “When DNA or data is being used or analyzed,” says Dr. Arbour, “it is the Indigenous communities that own that information. We are just the stewards of it.”
“This was causing a huge disparity in terms of access to care”
The IBVL, which is expected to be available by March 2024, will be a reference database with the population frequency of DNA variants present in Indigenous participants from diverse communities across Canada. It will be accessible to registered, approved users (across Canada and beyond) for the purpose of improving genetic diagnosis for Indigenous patients. The development of the IBVL has been guided by an Indigenous steering committee, taking into consideration Indigenous sovereignty principles.
From the bench to the bedside
One of the co-leads on the Silent Genomes Project is surgeon Dr. Nadine Caron, the First Nations Health Authority Chair in Cancer and Wellness at UBC, and the Director of the UBC Centre for Excellence in Indigenous Health. She noted a topic emerging more often at surgery conferences she was attending was the use of genomics in cancer screening and diagnostic testing — yet, there was the absence of Indigenous participation or opportunities in this space.
One of the co-leads on the Silent Genomes Project is surgeon Dr. Nadine Caron, the First Nations Health Authority Chair in Cancer and Wellness at UBC, and the Director of the UBC Centre for Excellence in Indigenous Health.
“This was causing a huge disparity in terms of access to care,” says Dr. Caron. “If we think, for example, of rare, familial or genetic-based cancers: We target tumours with a scalpel, but once the tumours are excised, they are looked at under a microscope. For those who have had access to genomic research and populations that are included in these background variant libraries, their tumours can also be evaluated at the genomic level. Indigenous communities have clearly been excluded from the research and these clinical tools.”
Through her many years in practice, Dr. Caron has seen issues surrounding access to care for both Indigenous and non-Indigenous communities alike. Yet, as an Indigenous scholar and surgeon — and a member of the Ontario Sagamok Anishnawbek First Nation — she also knows first-hand the sort of gaps within First Nations communities and other Indigenous populations the Silent Genomes Project looks to address. The first step in this process is the same as with any physician-patient relationship: building trust.
“One thing to recognize is how to build trust within these communities where there isn’t any,” she says, “and to rebuild trust where trust was broken. But speaking as an Indigenous person in Canada, I think it’s important that we not just assume that mistrust exists within these communities. It’s actually a major barrier to assume that there is mistrust, when we haven’t been given a chance to build trust in the first place.”
For Dr. Caron, a big part of the project’s success has been recognizing that cultural humility and cultural safety cannot be part of just one aspect of the care that Indigenous peoples receive. Instead, these elements need to be part of the entire chain, what she calls “from bench to bedside” — meaning from the research and laboratory work all the way to the point of care between physician and patient. “What we want to make clear to Indigenous patients, families and communities is this: You deserve access to a culturally safe experience from everyone in that chain,” she says, “from the researcher working to develop treatments to the intake nurse you meet at the door and the doctor providing your care at the beside.”
The circle of continuous conversation
One of the researchers involved in the project is Dr. Lauren Chad, a staff physician in the Division of Clinical and Metabolic Genetics at The Hospital for Sick Children and an associate professor of Paediatrics at the University of Toronto.
Another great success of the Silent Genomes Project is that it has built a whole network of researchers and Indigenous colleagues to ensure the Indigenous Background Variant Library becomes a rich trove of relevant data to make a precise diagnosis part of Indigenous patients’ care. The challenge for many researchers involved in this work, however, is that it’s a model where engagement with the participating communities needs to remain ongoing. “I call it the continuous conversation,” says Dr. Arbour. “It’s often challenging, but the relationship-building matters, so these circles of conversation never really end.”
One of the researchers involved in the project is Dr. Lauren Chad, a staff physician in the Division of Clinical and Metabolic Genetics at The Hospital for Sick Children and an associate professor of Paediatrics at the University of Toronto. She says that the Silent Genomes Project, with its intersection of Indigenous cultural safety, bioethics and paediatric care, has been a hugely important initiative in Canadian medical research.
“It’s really exciting to see this kind of precision diagnosis coming to patients of Indigenous descent,” says Dr. Chad. One of the key successes of the Silent Genomes Project, she adds, will be to increase access to care through a strong Indigenous-led governance model in concert with cultural competency training for the medical researchers and clinicians involved.
Another physician-researcher involved is Dr. Sonia Anand, a professor in the Department of Medicine at McMaster University and a senior scientist at the Population Health Research Institute at Hamilton Health Sciences. She agrees that a strong, Indigenous-led governance model has been key to the Silent Genomes Project’s success. It’s a model, she says, that goes beyond the concept of “nothing about us without us.” It’s about engaging with community members on an ongoing basis, ensuring that they have a primary role in conversations at every step of the project.
A professor in the Department of Medicine at McMaster University and a senior scientist at the Population Health Research Institute at Hamilton Health Sciences.
“This can be challenging for some researchers,” says Dr. Anand, “because it’s not as if you have one conversation with the community, get their approval on the goals of the research, get their DNA samples and then you’re done. There’s no algorithm to follow to get this right. It’s an ongoing discussion, an ongoing relationship. If there’s a change in leadership within the Indigenous community, then you need to restart those conversations with the new leaders and build that trust once again. You must make a longstanding commitment to working with these communities.”
Much of the governance model involves the concept known as “Ownership, Control, Access and Possession,” or OCAP© for short. Dr. Anand says bio specimens used in the Silent Genomes Project are held in trust — that is, each community owns their own biospecimens and researchers associated with the project hold them in trust. There is also recognition that there may not be consensus among individuals within a single community: some may, for example, want the samples to be used strictly as intended for the research at hand; others may be fine with their biospecimens being used in other research that may benefit their community and Indigenous people more broadly. The OCAP model is meant to ensure there is Indigenous-led governance at every stage of the process.
What does success look like?
With such a huge undertaking, there are many ways to measure success for the Silent Genomes Project. For project lead Dr. Arbour, success will mean doctors across the country will make using the IBVL a standard part of medical genetics care for Indigenous patients with rare genetic diseases, and the conversations addressing barriers to care continue with Indigenous patients, families and communities. “The project itself is finite,” she says, “but we’ll know we’ve succeeded when we keep the dialogue going and physicians use the Background Variant Library to provide the care that Indigenous patients deserve.”
Success will mean doctors across the country will make using the IBVL a standard part of medical genetics care for Indigenous patients with rare genetic diseases
For Dr. Caron, the success of the Silent Genomes project will be something much broader and more far-reaching — for her own Indigenous community and others that she serves. “Real success would be to share what we’ve learned in terms of process from all these wise, wise Indigenous people from across the country and apply it in other areas,” she says. “My definition of success was never simply that the Background Variant Library would be created, but that real choice would be given to Indigenous communities about whether they wanted to be a part of it. Real equity is about no longer being invisible; it’s about having the choice to be part of something.”
Key Highlights
- Indigenous genomic reference data, needed for accurate diagnosis, is not represented in commonly used public databases built through research.
- The Silent Genomes Project is a game-changing effort to address this inequity, by bringing life-changing genomic diagnosis to Indigenous patients of all ages, while ensuring Indigenous-led governance over biological samples and health data.
- The Silent Genomes Project is establishing processes with Indigenous partners for safe governance of genomic data and is culminating with the development of an Indigenous Background Variant Library (IBVL) with the goal of improved diagnosis for genetic conditions.
- The IBVL, expected to be available by March 2024, will be a reference database with the population frequency of DNA variants present in Indigenous participants from diverse communities across Canada.
- The IBVL will aid in interpretation of genomic sequencing for rare diseases, and also for Indigenous patients undergoing panel genetic sequencing for specific disorders such as hereditary cancer, inherited arrhythmias, cardiomyopathy, seizures and other genetic testing panels commonly used.
- Success will mean doctors across the country will make using the IBVL a standard part of medical genetics care for Indigenous patients with genetic diseases, and the conversations addressing barriers to care continue with Indigenous patients, families, and communities.
