Genetic architecture of age-related cognitive decline in African Americans

Towfique Raj, Lori B. Chibnik, Cristin McCabe, Andus Wong, Joseph M. Replogle, Lei Yu, Sujuan Gao, Frederick W. Unverzagt, Barbara Stranger, Jill Murrell, Lisa Barnes, Hugh C. Hendrie, Tatiana Foroud, Anna Krichevsky, David A. Bennett, Kathleen S. Hall, Denis A. Evans, Philip L. De Jager

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19 Scopus citations


Objective: 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.

Original languageEnglish
Article numbere125
JournalNeurology: Genetics
Issue number1
StatePublished - 2016


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