Transferability of a European-derived Alzheimer’s Disease Genetic Risk Score across Multi-Ancestry Populations.

Abstract We built a genetic risk score (GRS) from the most complete landscape of the Alzheimer disease (AD) genetics. We extended its analysis in 16 European countries and observed a consistent association of this GRS with AD risk, age at onset and cerebrospinal fluid (CSF) AD biomarker levels regardless of the Apolipoprotein E (APOE) genotype. This GRS was also associated with AD risk (independently of APOE) with a decreasing order of magnitude in those with an European-American, North-African, East-Asian, Latin-American, African-American sub-Saharan African and Indian background respectively. No association of the GRS to AD was seen in sub-Saharan African and Indian populations. This GRS captures information specific to AD as its association decreases as the diagnosis broadens. In conclusion, a simple GRS captures shared genetic information specific to AD between multi-ancestry populations. However, more population diversity is needed to better understand the AD genetic complexity across populations.