Alzheimer disease (AD), essentially the most common neurodegenerative disorder on the planet, affects individuals of all races and ethnicities; nonetheless, most genetic research for AD has been performed on individuals of European ancestry (EA) with a limited variety of large-scale genetic studies in other populations.

For a lot of centuries, Ashkenazi Jews lived in communities in Eastern Europe and were genetically isolated from their non-Jewish neighbors. Because of this, researchers from Boston University Chobanian & Avedisian School of Medicine hypothesized that some AD susceptibility variants are more frequent, and thus more prone to show statistically significant associations, on this group in comparison with much larger and more genetically heterogeneous EA cohorts.

Our study illustrates the greatly increased power for detection of genetic associations in communities like Ashkenazi Jews who trace their lineage to a comparatively small group of ancestors. In such communities, disease-associated variants could also be rather more frequent in comparison with samples ascertained from large, mixed populations.”

Lindsay A. Farrer, PhD, chief of biomedical genetics, corresponding writer

Farrer and his colleagues conducted a genome-wide association study for AD in a sample of roughly 3,500 individuals whose ancestry was almost exclusively Ashkenazi Jewish including roughly equal numbers of individuals with AD and cognitively normal individuals who were identified in a much larger group of EA 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 aspects for AD including some previously known (APOE, TREM2) and a number of other novel ones which are strong biological candidates (RAB3, SMAP2, ZNF890P, SPOCK3, GIPR).

In keeping with 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 comparatively small group of ancestors. “Some genetic association signals for complex diseases like AD are prone to be stronger in founder populations which are relatively genetically homogeneous,” said Farrer.

Although a few of the findings in Ashkenazi Jews weren’t observed in other populations due to rarity or absence of those genetic variants in those groups, Farrer believes the contribution of the genes harboring these variants to AD biology is probably going relevant to other major populations on the planet. “Future studies focused on the AD-associated genes identified on this study may result in the event of novel AD biomarkers and therapeutic targets,” he said.

These findings appear online within the publication Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Source:

Boston University School of Medicine

Journal reference:

Li, D., et al. (2023) Novel loci for Alzheimer’s disease identified by a genome-wide association study in Ashkenazi Jews. Alzheimer s & Dementia. doi.org/10.1002/alz.13117.