LOS ANGELES ― The vast majority of people in genetic epilepsy studies are of white, European ancestry, skewing the genetic evidence used to guide diagnosis, management and understanding of epilepsy. This likely leads to missed epilepsy risk factors and less-equitable care for those of non-European descent, suggests a first-of-its-kind study of more than 3 million people presented at the American Epilepsy Society Annual Meeting.
The researchers analyzed the findings of 68 genome-wide association studies, which scanned all participants’ genomes to identify variations associated with epilepsy: genetic markers called single nucleotide polymorphisms (SNPs) that may increase the risk of the condition. They determined that overall, only 8% of people with epilepsy who participated in these studies were of non-European descent, which included those with ancestors from East Asia (China, Japan, Korea, Mongolia and Taiwan) or Africa (including African Americans). None of the participants were of admixed American (including Native Americans and Hispanics, who are of mixed European and Native American ancestry), Native American or South Asian (India, Pakistan, Bangladesh, Nepal, Sri Lanka, Bhutan and the Maldives) descent.
“Epilepsy affects people from all walks of life and ethnicities, but the genetics research that informs diagnosis and management of epilepsy has overwhelmingly focused on individuals of European descent,” said Chethan Rao, DO, MS, lead author of the study and assistant professor of pediatric neurology at the University of Maryland, Baltimore. “By expanding these studies to include more diverse populations, we may also uncover genetic insights that not only improve care for underrepresented groups but also broaden our understanding of epilepsy as a whole.”
Genome-wide association studies help scientists identify genetic patterns to create polygenic risk scores (PRS), which determine a person’s risk of epilepsy based on their genes. The PRS is most accurate for people from groups well-represented in studies. Due to the lack of diversity in these studies, the PRS is less accurate in people who have non-European ancestry.
Researchers reviewed genome-wide association studies on epilepsy published between 2010 and 2024. The researchers assessed ancestry based on the 1000 Genomes Project categories: admixed American, African, European, East Asian and South Asian. Of the 3,574,909 total participants in the studies, 293,725 had epilepsy (cases) and 3,281,184 did not (controls).
They determined that overall, 71.5% of the study participants were of European ancestry, 14.3% were East Asian, 0.5% were African, and none were South Asian or admixed American. However, ancestry was not reported for 13.7% of participants. Among those with epilepsy, only 8% were of non-European ancestry: 6.4% were East Asian and 1.5% were African.
The lack of diversity in the studies likely led to missing important findings. Overall, 98 unique SNPs were identified as statistically significant. Studies of participants who exclusively had European ancestry comprised 66% of all studies, yet those studies contributed only 21% of the significant SNPs. Conversely, studies that included participants of non-European ancestry comprised only 16% of studies but identified 58% of significant SNPs. This shows that the power to detect genetic variation strongly linked to epilepsy is lower in European ancestry, underscoring that improving diversity is not only an ethical imperative, but also a scientific need.
“To our knowledge, this is the first study to assess diversity in epilepsy genome-wide association studies. Despite the growing awareness of the need for diversity, the rate of non-European genome studies is increasing slower than that of European-ancestry studies, widening the disparity,” said Dr. Rao. “The lack of diversity in epilepsy genome-wide association studies means we don’t have the knowledge we need to most effectively treat diverse populations, including learning more about the genetic information that can help guide the development of drugs that work better for people of non-European ancestry.”
The lack of diversity is due to several factors, said Dr. Rao. An estimated 72% of participants in all genome-wide studies are from Iceland, the United Kingdom and the United States, where most research is conducted and funded. Additionally, there’s often a lack of trust in genetic research from non-European communities due to historical exploitation. Further, while there are efforts to improve genomic diversity on commercially available genotyping arrays, non-European heritage references, databases and analytical tools are still lagging. As a result, researchers don’t have as easy access to the tools they need to analyze data from non-European ancestry participants, so they’re often excluded from the study results.
He noted that correcting this disparity requires:
- investment in genomics in low- and middle-income countries, such as the H3Africa research initiative,
- diversifying the genomics workforce by training and supporting researchers from diverse backgrounds and
- ensuring that data from diverse populations are accessible to researchers globally.
*** AES 2024 news releases may contain updated data that does not match what is reported in the abstract.