Do Alzheimer's genetic risk markers identified in Europeans also relate to memory in people in India?

Details

Genetic factors play an important role in Alzheimer's disease (AD) and cognitive aging. But it is unclear whether risk loci identified in European ancestry (EA) populations have similar effects in other groups, including South Asians.

This genetic association study examined the allele distribution and cognitive associations of 56 known AD risk single-nucleotide polymorphisms (SNPs), identified in three EA genome-wide association studies (EA-GWASs), in a South Asian population. Researchers assessed associations of individual SNPs and combined genetic risk scores (GRSs) with measures of episodic memory.

The study used the Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). It included 906 LASI-DAD participants from diverse states in India. Participants were genotyped using the Illumina Global Screening Array, with imputation using 1000G Phase 3v5. Cognitive measures included total learning and delayed word recall.

Only a few SNPs were significantly associated with memory scores (P < .05). However, effect estimates from the EA-GWASs and LASI-DAD showed moderate correlation (0.35–0.88) in the expected direction. GRSs were also associated with memory scores, but the percentage of variation explained was small (0.1%–0.6%).

Differences in allele frequencies and cognitive association results suggest that genetic factors identified predominantly through EA-GWASs may play a limited role in South Asians. However, the extent of differences between EA and South Asian populations in the genetic architecture of AD and cognition remains uncertain. The researchers also emphasized a critical need for a more comprehensive assessment of the mutational spectrum in South Asia to identify new genetic variants associated with AD and cognition in this population.

Publication: J Am Geriatr Soc 68:S45–S53, 2020.