Studying the genomes of Ashkenazi Jewish people and other closely related groups may bolster Alzheimer’s research
Scientists found both potentially new and previously discovered Alzheimer’s disease genetic risk factors by analyzing the genomes of a relatively small group of people who were identified as being of Ashkenazi Jewish ancestry. The results from the NIA-funded study, published in Alzheimer’s & Dementia, suggest that genomic studies of Ashkenazi Jewish people and other closely related “genetic founder” groups may help clarify the genetic basis for Alzheimer’s.
People of Ashkenazi ancestry descend from a population of Jewish people who founded communities in Central and Eastern Europe during the Middle Ages. For many centuries, Ashkenazi Jewish communities in Europe were culturally isolated from non-Jewish Europeans, and as a result, the population is genetically distinct from non-Jewish Europeans. Due to this reduction in genetic variation, or “founder effect,” several hereditary diseases and types of cancer are found predominantly or more frequently in people of Ashkenazi Jewish descent. In this study, the researchers hypothesized that Alzheimer’s disease genetic risk factors may appear more frequently — and thus be easier to identify — than in broader, more genomically diverse European populations.
Led by scientists at Boston University, the researchers used genomic information about the Ashkenazi Jewish population to analyze data of three different large genomic and genetic Alzheimer’s disease studies involving more than 80,000 participants of European descent. More than 6,500 individuals appeared to be of Ashkenazi Jewish descent. Approximately 2,800 of these people were diagnosed with Alzheimer’s and about 3,700 were not.
By comparing those who had Alzheimer’s with those who did not, the researchers found previously identified risk factors such as variants of genes called APOE and TREM2. The APOE associations were relatively strong given the small sample size. They also found several potential new risk factors that had borderline levels of association with Alzheimer’s. For example, one was found linked to a gene called RAB3B, which is involved in the release of dopamine, an important chemical signal in the brain.
Experiments on autopsied brain tissue provided further support for the idea that the variants identified by this analysis are Alzheimer’s disease genetic risk factors. The researchers note that studying a population with very similar genetics enabled them to uncover new genes that would have been hard to identify in a genetically heterogeneous population.
Further studies are needed to confirm these findings and potentially identify other genetic changes associated with Alzheimer’s in people of Ashkenazi Jewish descent or in other historically isolated populations.
This research was supported in part by NIA grants P30AG072978, RF1AG057519, R01AG048927, U01AG032984, U54AG052427, P30AG072878, U19AG068753, U01AG058654, and U01AG062602.
These activities relate to NIH’s Alzheimer’s and Related Dementias Research Implementation Milestone 2.G, “Maximize the translational potential of genetics research by ensuring rapid and broad sharing of large-scale genetic/genomic data.”
Reference: Li D, et al. Novel loci for Alzheimer’s disease identified by a genome-wide association study in Ashkenazi Jews. Alzheimer’s & Dementia. 2023. Epub June 1. doi: 10.1002/alz.13117.