Genetic architecture of age-related cognitive decline in African Americans
Replogle, Joseph M.
Unverzagt, Frederick W.
Hendrie, Hugh C.
Bennett, David A.
Hall, Kathleen S.
Evans, Denis A.
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CitationRaj, T., L. B. Chibnik, C. McCabe, A. Wong, J. M. Replogle, L. Yu, S. Gao, et al. 2016. “Genetic architecture of age-related cognitive decline in African Americans.” Neurology: Genetics 3 (1): e125. doi:10.1212/NXG.0000000000000125. http://dx.doi.org/10.1212/NXG.0000000000000125.
AbstractObjective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.
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