PT  - JOURNAL ARTICLE
AU  - Towfique Raj
AU  - Lori B. Chibnik
AU  - Cristin McCabe
AU  - Andus Wong
AU  - Joseph M. Replogle
AU  - Lei Yu
AU  - Sujuan Gao
AU  - Frederick W. Unverzagt
AU  - Barbara Stranger
AU  - Jill Murrell
AU  - Lisa Barnes
AU  - Hugh C. Hendrie
AU  - Tatiana Foroud
AU  - Anna Krichevsky
AU  - David A. Bennett
AU  - Kathleen S. Hall
AU  - Denis A. Evans
AU  - Philip L. De Jager
TI  - Genetic architecture of age-related cognitive decline in African Americans
AID  - 10.1212/NXG.0000000000000125
DP  - 2017 Feb 01
TA  - Neurology Genetics
PG  - e125
VI  - 3
IP  - 1
4099  - http://ng.neurology.org/content/3/1/e125.short
4100  - http://ng.neurology.org/content/3/1/e125.full
SO  - Neurol Genet2017 Feb 01; 3
AB  - 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.AA=African American; AD=Alzheimer disease; CHAP=Chicago Health and Aging Project; EA=European ancestry; GWAS=genome-wide association study; IIDP=Indianapolis-Ibadan Dementia Project; MAP=Rush Memory and Aging Project; MARS=Minority Aging Research Study; ROS=Religious Orders Study; SNP=single nucleotide polymorphism