Alzheimer's Disease Polygenic Risk Score Transferable Across European, Korean Populations

A polygenic risk score (PRS) for Alzheimer's disease-related dementia that was derived from European ancestry data was also effective in identifying Korean individuals at high risk for the condition, a study appearing this week in JAMA Network Open has found. Research has shown that PRSs can help distinguish individuals at high genetic risk for Alzheimer's disease, but the data used to build these scores has largely come from studies in populations of European ancestry. As a result, the generalizability of such PRSs to non-European individuals is unclear. To investigate, researchers from Sungkyunkwan University in South Korea and elsewhere developed a PRS based on a large-scale genome-wide association study (GWAS) involving around 22,000 people of European descent with Alzheimer's disease and almost 42,000 controls. The PRS was then tested in roughly 1,600 Korean individuals. The researchers found that the PRS was associated with high genetic risk for Alzheimer's disease dementia in the Korean individuals, as well as with amnestic mild cognitive impairment, earlier symptom onset of AD dementia, and amyloid-beta deposition. They additionally evaluated a PRS based on a GWAS of a Japanese population, which they found to have a low performance, likely due to the sample size. A PRS based on a transancestry meta-analysis of European and Japanese GWASs, meanwhile, had improved accuracy. "Our findings emphasize the ancestral transferability and clinical value of the PRS," the authors write.