Raj, TowfiqueChibnik, LoriMcCabe, CristinWong, AndusReplogle, Joseph M.Yu, LeiGao, SujuanUnverzagt, Frederick W.Stranger, BarbaraMurrell, JillBarnes, LisaHendrie, Hugh C.Foroud, TatianaKrichevsky, AnnaBennett, David A.Hall, Kathleen S.Evans, Denis A.De Jager, Philip2017-02-182016Raj, 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.0000000000000125.2376-7839http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371171Objective: 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.en-USJournal Article2017-02-1810.1212/NXG.0000000000000125