Unique genetic risk factors for Alzheimer’s discovered in Ashkenazi Jews

Researchers from Boston University found the new markers by studying Americans with East European Jewish heritage.

The historic isolation of East European Jews makes them a natural laboratory for genetic study.

Researchers at Boston University have now used this population to isolate Alzheimer’s disease variants, some of which have never been found before.

The researchers hypothesised that some Alzheimer’s susceptibility variants are more frequent and thus more likely to show statistically significant associations in a relatively homogenous group.

They conducted a genome-wide association study for Alzheimer’s in a sample of approximately 3500 individuals whose ancestry was almost exclusively Ashkenazi Jewish, comparing Ashkenazi Jews with Alzheimer’s to a control Ashkenazi Jewish population.

The researchers identified several genetic risk factors for Alzheimer’s including some previously known (APOE, TREM2) and several novel ones that are strong biological candidates (RAB3, SMAP2, ZNF890P, SPOCK3, GIPR).

Author Lindsay A. Farrer, who is chief of biomedical genetics at Boston University, said some genetic association signals for complex diseases like Alzheimer’s were likely to be stronger in populations that are relatively genetically homogeneous, making it easier for researchers to identify the relevant genetic markers.

“Our 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. In such communities, disease-associated variants may be much more frequent compared to samples ascertained from large, mixed populations,” Dr Farrer said.

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 harbouring these variants to Alzheimer’s disease biology is likely to be 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.

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

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Unique genetic risk factors for Alzheimer’s disease discovered in Ashkenazi Jews (Studyfinds)

Full paper: Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews (Wiley)

Photo: Cleveland Jewish Federation