Diagnosis of complex genetic diseases is a global challenge, but genomics research remains disproportionately focused on populations of European ancestry. Inclusive, diverse research could unlock the door to new therapies, says Neil Ward, VP of PacBio EMEA.
Europeans make up less than 20% of the world’s population but represent more than 90% of participants in publicly available genome-wide association studies (GWAS).
In contrast, Asian populations, which comprise around 60% of the global population, contribute just 10%. Meanwhile, African populations account for just 2% of GWAS data.
Limited genomic datasets have stunted scientists’ understanding of how certain diseases present and progress in people of non-European ancestry. As a result, diagnostics and treatments are often based on a ‘one-size-fits-all’ model, which may be less effective for underrepresented groups and reinforce existing health inequities.
One area impacted by this inequality is neurodegenerative disease. By 2050, global dementia cases are expected to triple to 139 million, yet currently, 3 in 4 people don’t receive a formal diagnosis of their specific disease.
This is partly due to the limitations in healthcare infrastructure in lower income countries, but also because of the disease’s complexity and that existing datasets are overwhelmingly Eurocentric.
But there is cause for optimism. Advances in genomic sequencing technology are lowing the barriers to entry for studying dementia-related diseases and enhancing genomic insights in diverse populations.
Greater understanding of genetic underpinnings of disease will allow scientists to develop more inclusive, effective diagnostics and treatment routes.
Technologies closing the diversity gap
Accurate long-read sequencing holds transformative potential for scientists’ understanding of complex neurodegenerative diseases.
Most dementia-related diseases are associated with multiple genetic variations, many of which are found in the hard-to-sequence regions of the genome.
Traditional short-read sequencing methods often misinterpret or miss these crucial variants due to the limitation of sequencing small sections of DNA. As a result, clinicians have long struggled to identify the genetic underpinnings of cognitive decline, making it difficult to diagnose or treat disease progression.
In contrast, long-read sequencing captures longer, more complex variations in a single read, providing researchers with a clearer view of regions of the genome where neurodegenerative diseases are believed to start.
The most advanced long-read technologies make it possible to gain even deeper insights into the biology of neurodegenerative disease by revealing epigenetic information, such as methylation.
Understanding subtle patterns in this rich source of information is important, as many early changes indicative of disease often appear in this biological layer first.
Thanks to leaps in the speed and affordability of long-read sequencing, it is becoming increasingly feasible for countries who have not previously done so to invest in larger-scale genomic projects that investigate how neurodegenerative diseases impact their populations.
The cost of running a long-read genomics test has decreased from over $100 million in 2001 to under $500 today. At the same time, sequencing capacity has grown dramatically, with a single machine processing up to 1,300 samples per year.
A regional model for inclusive genomics
One example of shifting the Eurocentric lens of neurodegenerative diseases is the North African Dementia Registry (NADR). The Registry is a collaboration between non-profit Davos Alzheimer’s Collective, University College London, the American University in Cairo and PacBio.
It aims to build a high-quality, comprehensive multi-omics dataset to allow researchers the opportunity to explore new insights into the genetic and environmental factors contributing to Alzheimer’s disease and other dementia-related diseases.
The first of its kind in North Africa, the project is based in Egypt, which serves as a unique bridge between the Middle East and Africa, offering a rich tapestry of genetic diversity.
By working to extend Alzheimer’s and brain health research to underrepresented groups, the project will build upon findings and actively engage with populations to fill the gaps in knowledge of how dementia manifests in different ancestries.
The hope is that the NADR will uncover more variants like the APOE ε3 R145C variant, which is present in more than 4% of African Americans but rarely in people of European descent. When paired with the ε4 allele, the R145C variant triples the likelihood of those of African descent developing Alzheimer’s.
Knowledge like this underscores the need to diversify research and the risks associated with relying on our current datasets.
The future of dementia research is diverse
As neurodegenerative diseases like Alzheimer’s continue to impact people at an alarming rate, diverse genomics holds the key to reducing the global burden of these diseases and unlocking new therapies.
To achieve the depth of analysis required to understand such complex genetic conditions, greater investment in long-read sequencing is required. Equally important is the need for deep and sustained partnerships with universities and research institutions that bring local expertise and are trusted by the communities they serve.
To boost participation from the public, there must be further investment in education and raising awareness around why their involvement in genomics projects matters, including how it will contribute to their future health and broaden research diversity.
Without new contributions, there is a significant risk of building a stunted future of medicine that only works for some. But with broader input, diverse datasets can be built that will help tackle the growing issue of neurogenerative diseases and equitably improve worldwide health.
