Genetic architecture of age-related cognitive decline in African Americans

Autor: Towfique Raj, Frederick W. Unverzagt, Lisa L. Barnes, Tatiana Foroud, Lei Yu, Jill R. Murrell, Hugh C. Hendrie, Cristin McCabe, Joseph M. Replogle, Barbara E. Stranger, Andus Hon-Kit Wong, David A. Bennett, Sujuan Gao, Denis A. Evans, Philip L. De Jager, Kathleen S. Hall, Lori B. Chibnik, Anna M. Krichevsky
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Neurology: Genetics
ISSN: 2376-7839
Popis: 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.
Databáze: OpenAIRE
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