Genetic susceptibility to accelerated cognitive decline in the US Health and Retirement Study.
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.
Department of Health Studies, University of Chicago, Chicago, IL, USA.
Chenan
C
Zhang
Department of Health Studies, University of Chicago, Chicago, IL, USA; University of Chicago Comprehensive Cancer Center, Chicago, IL, USA. Electronic address: brandonpierce@uchicago.edu.
Brandon L
BL
Pierce
D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D003430:Cross-Sectional Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D014481:United States
D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
APOE; Cognitive decline; Genome-wide association study; Heritability; TOMM40