A recent study conducted by researchers from the Boston University Chobanian & Avedisian School of Medicine has identified several new genetic risk factors for Alzheimer’s disease (AD) that are unique to Ashkenazi Jews.
AD is the most common neurodegenerative disorder in the world, affecting individuals of all races and ethnicities. However, most genetic research for AD has been performed on individuals of European ancestry, with a limited number of large-scale genetic studies conducted on other populations.
For many centuries, Ashkenazi Jews lived in communities in Eastern Europe and were genetically isolated from their non-Jewish neighbors. The researchers hypothesized that some AD susceptibility variants are more frequent, and thus more likely to show statistically significant associations, in this group compared to much larger and more genetically heterogeneous European ancestry cohorts.
The study conducted a genome-wide association study for AD in a sample of approximately 3,500 individuals whose ancestry was almost exclusively Ashkenazi Jewish. This included roughly equal numbers of persons with AD and cognitively normal individuals who were identified in a much larger group of European ancestry participants in large national AD genetics studies using an approach that compared genetic signatures with members of an Ashkenazi Jewish reference sample.
The researchers identified several genetic risk factors for AD, including some previously known (APOE, TREM2) and several novel ones that are strong biological candidates (RAB3, SMAP2, ZNF890P, SPOCK3, GIPR).
According to the researchers, this study illustrates the greatly increased power for detection of genetic associations in communities like Ashkenazi Jews who trace their lineage to a relatively small group of ancestors. “Some genetic association signals for complex diseases like AD are likely to be stronger in founder populations that are relatively genetically homogeneous,” said Lindsay A. Farrer, PhD, chief of biomedical genetics and corresponding author of the study.
Although some of the findings in Ashkenazi Jews were not observed in other populations because of the rarity or absence of these genetic variants in those groups, Farrer believes the contribution of the genes harboring these variants to AD biology is likely relevant to other major populations in the world. “Future studies focused on the AD-associated genes identified in this study may lead to the development of novel AD biomarkers and therapeutic targets,” he said.
In conclusion, this study highlights the importance of studying genetic susceptibility in diverse populations and illustrates the potential of founder populations to detect significant genetic associations for complex diseases like AD. The identification of these novel genetic risk factors for AD may inform the development of new biomarkers and therapies for this devastating disease.
