Title |
Genetic architecture of age-related cognitive decline in African Americans
|
---|---|
Published in |
Neurology: Genetics, December 2016
|
DOI | 10.1212/nxg.0000000000000125 |
Pubmed ID | |
Authors |
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 |
Abstract |
To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 5 | 50% |
Sweden | 1 | 10% |
Unknown | 4 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 50% |
Scientists | 4 | 40% |
Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 31 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 10 | 32% |
Professor > Associate Professor | 4 | 13% |
Student > Ph. D. Student | 3 | 10% |
Other | 2 | 6% |
Student > Doctoral Student | 2 | 6% |
Other | 4 | 13% |
Unknown | 6 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 7 | 23% |
Neuroscience | 3 | 10% |
Psychology | 3 | 10% |
Medicine and Dentistry | 3 | 10% |
Economics, Econometrics and Finance | 2 | 6% |
Other | 5 | 16% |
Unknown | 8 | 26% |