Genetic susceptibility to accelerated cognitive decline in the US Health and Retirement Study.

TitleGenetic susceptibility to accelerated cognitive decline in the US Health and Retirement Study.
Publication TypeJournal Article
Year of Publication2014
AuthorsZhang, C, Pierce, BL
JournalNeurobiol Aging
Date Published2014 Jun
ISSN Number1558-1497
KeywordsAfrican Americans, Aged, Aged, 80 and over, Chromosomes, Human, Pair 9, Cognition, Cognition Disorders, Cross-Sectional Studies, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Transport Proteins, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, United States

Age-related cognitive decline is a major public health concern facing a large segment of the US population. To identify genetic risk factors related to cognitive decline, we used nationally representative longitudinal data from the US Health and Retirement Study to conduct genome-wide association studies with 5765 participants of European ancestry, and 890 participants of African ancestry. Mixed effects models were used to derive cognitive decline phenotypes from data on repeated cognitive assessments and to perform single nucleotide polymorphism-based heritability estimation. We found 2 independent associations among European-Americans in the 19q13.32 region: rs769449 (APOE intron; p = 3.1 × 10(-20)) and rs115881343 (TOMM40 intron; p = 6.6 × 10(-11)). rs769449 was also associated with cognitive decline among African-Americans (p = 0.005), but rs115881343 was not. Cross-sectional cognitive function showed moderate heritability (15%-32%) across several age strata (50-59, 60-69, 70-79 years), but the cognitive decline heritability estimate was low (∼5%). These results indicate that despite multiple association signals for cognitive decline in the 19q13.32 region, inter-individual variation is likely influenced substantially by environmental factors.

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Alternate JournalNeurobiol. Aging
Citation Key8622
PubMed ID24468470