Silent genomes: Reducing health care disparities and improving diagnostic success for children with genetic diseases from Indigenous populations

Health Research BC is providing match funds for this research project, which is funded by the Genome Canada/CIHR Large-Scale Applied Research Project (LSARP): Genomics and Precision Health funding opportunity. Additional support is provided by Genome BC, the BC Children’s Hospital Foundation, BC Provincial Services Health Authority and the University of British Columbia (UBC).

Indigenous populations in Canada and around the world face unique health challenges, inequities, and barriers to healthcare. As a result, they typically have poorer health outcomes than non-Indigenous groups.

The health disparity gap widens when it comes to Indigenous populations’ access to the technology and research involved in genomics – the study of the complete set of human genes – which have advanced health care by allowing medical treatments to be tailored to the specific needs of individual patients through precision medicine, routinely available to other Canadians.

Dr. Laura Arbour, a clinical geneticist at BC Children’s Hospital and Island Health, and a professor in UBC’s Department of Medical Genetics, is working to address the growing genomic divide – particularly the lack of background genetic variation data for Indigenous populations – through the Silent Genomes project. The four-year project aims to improve health outcomes by reducing health disparities, enhancing equitable access to diagnosis, treatment, and care for Indigenous children with genetic diseases. Arbour is joined on the project by the University of Northern British Columbia’s Dr. Nadine Caron, and Dr. Wyeth Wasserman from UBC and the BC Children’s Hospital Research Institute, where the research will be conducted, along with BC Women’s Hospital + Health Centre.

The Silent Genomes research team will work with First Nations, Inuit and Métis partners across Canada to establish processes for Indigenous-led governance of biological samples and genome data, leading to policy guidelines and best practice models for genomic research and clinical care.

The project will also create an Indigenous Background Variant Library (IBVL) of genetic variation from a pool of 1,500 First Nations Canadians that will improve the accuracy of genomic diagnosis by providing necessary reference data for Indigenous populations living in Canada and globally. Researchers will also assess the effectiveness of the IBVL to lower health care costs, and plan for long-term use of the IBVL for Canadian Indigenous children and adults needing genetic/genomic health care.

End of Award Update – July 2024

Results:

The Silent Genomes Project (SGP) successfully achieved four main objectives:

1. Established Indigenous-informed policies for Indigenous governance over biological data through the S-GIRDD Steering Committee.
2. Developed a comprehensive Background Variant Library (IBVL) using genomic data from First Nations participants, that was operational in January 2024, allowing internal testing with potential for expansion with more genomes from Indigenous participants.
3. Conducted whole genome sequencing for Indigenous patients with suspected genetic diseases, with standard analysis completed for 89 patients/families and ongoing analysis for unresolved cases.
4. Provided research training for Indigenous students in precision diagnosis and health economics over a six-year period. With the scholarship support of Life labs, the project team ensured the participation of over 30 students in the first 5 SING Canada workshops.

Impact:

1. Governance within the Silent Genomes Project ensured development of policies and operational guidelines for Indigenous involvement in genomic research. The Silent Genomes Indigenous Rare Disease Diagnosis Steering Committee has developed the processes for variant release which were implemented for the IBVL, protocols for clinical research applications planning to use the IBVL, and review process for the manuscripts where IBVL was used for the variant selection. The process of transformation of the advisory S-GIRDD Steering Committee into the sustainable IBVL Governance Committee is underway. The project leadership and the S-GIRDD committee members participated in the 2nd “DNA on Loan” conference organized by CIHR, where gaps in currently existing guidelines, that the team was exposed through the SG lifetime, have been discussed. Internationally, utilizing the mechanism approved by the S-GIRDD (online restricted access to frequency of Indigenous variants) within accepted upon ethical frameworks (CARE principles), was reviewed and is under consideration by two other jurisdictions (Australia and New Zealand).
2. Efforts were made to enhance the capacity of healthcare providers, Indigenous patients, communities, and students to engage with genomics research and health care. Five SING Canada workshops were conducted by Dr. Tall bear and her team, with the support of SG team members. Additionally, two Indigenous graduate students have either completed or are nearing completion of their studies. Educational materials developed by Activity 1 are available on the Silent Genomes website, along with regularly updated content on Genetics and Genomics research best practices.
3. The first release of the Indigenous Background Variant Library (IBVL) is undergoing testing and will be available for clinical use within the next few months. Once completed, this effort will enable assessment of how genomic variant knowledge impacts diagnostic clarity for Indigenous patients with rare diseases. The SGIRDD Steering Committee is actively involved in developing sustainable IBVL usage processes beyond the project’s duration. Internationally, the pipeline and user interface developed within the project have been shared with the Varoomed Project (Aotearoa/New Zealand), for testing or partial adoption.
4. Aims to increase access to genetically based diagnoses and care involved closing enrollment and engaging National Clinical Network (NCN) teams across 11 Canadian sites, with ongoing discussions to address limitations in Canadian TCPS2 Chapter 9 guidelines. Efforts were made to raise awareness among healthcare providers regarding barriers to accessing clinical and research genomics post-project. The Culturally Informed Genetic Counselling Guide, provided to each site, has been published on the SG Best Practices website for wider dissemination. The NCN continues to work on breaking down barriers to access to clinical and research genomics.

Potential Influence:

1. The lessons learned while establishing a National Clinical Network will be used to break down barriers in access to clinical and research genomics for Indigenous peoples.
2. Further collaborations are needed to fill the existing gaps in policies and guidelines related to Indigenous involvement in genomic research.
3. The S-GIRDD Steering Committee is currently focused on developing processes for sustainable use of the IBVL beyond the Silent Genomes project, with the goal of independent continuous seamless governance and technical support during the lifetime of the IBVL.
4. The international “Be FAIR and CARE” meeting gathered international Indigenous Genomics specialists from around the world, which conceived an idea of creating an International Indigenous Genomics Advisory and Research Consortium which would provide the necessary skills and knowledge for the development of stipulations for Indigenous data sharing processes globally. If similar projects are using comparable pipelines and user interface (e.g. the ones developed within the project), it may technically ease global data sharing processes.
5. The Health Economics study developed a set of practical and collaborative approaches for qualitative research when working with Indigenous People and communities to provide opportunities to advance Indigenous governance, capacity, and equity approaches.

Next Steps:

Building upon the original SGP, the new extended work is intended to catalyze longer-term efforts that could be sustained under healthcare systems (as the reference data provided by the IBVL becomes standard of care for diagnostic testing), funded by grants such as an anticipated Genome Canada health competition, directly supported through federal allocation, or a mixture of these models. Over the next 5 years, there are four key foci. First, developing sustained funding for the IBVL as an integrated reference data source for clinical diagnosis of rare disease. Second, achieving broader inclusion of Indigenous communities in the IBVL to enable the reference data to be of equitable utility for all Indigenous peoples of Canada. Third, to build upon emerging capacity to substantially increase the number of Indigenous researchers, research leaders, and genetic/genomic health care providers. Fourth, to identify and develop new health-related applications requiring reference data that are of priority to Indigenous peoples.