Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores me...

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Published in:Alzheimer disease and associated disorders Vol. 30; no. 3; p. 195
Main Authors: Marden, Jessica R, Mayeda, Elizabeth R, Walter, Stefan, Vivot, Alexandre, Tchetgen Tchetgen, Eric J, Kawachi, Ichiro, Glymour, M Maria
Format: Journal Article
Language:English
Published: United States 01.07.2016
Subjects:
African Americans - genetics
Alzheimer Disease - genetics
Ethnic Groups
European Continental Ancestry Group - genetics
Female
Follow-Up Studies
Genome-Wide Association Study - methods
Humans
Male
Memory Disorders - genetics
Middle Aged
Risk Factors
United States
ISSN:1546-4156, 1546-4156
Online Access:Get more information
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Summary:Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26% faster than NHW decline (P<0.001). Among NHW, 10% higher AD-GRS predicted faster memory decline (linear β=-0.058 unit decrease over 10 y; 95% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear β=-0.050; 95% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.
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ISSN:1546-4156
1546-4156
DOI:10.1097/WAD.0000000000000137