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

TitleUsing an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.
Publication TypeJournal Article
Year of Publication2016
AuthorsMarden, JR, Mayeda, ER, Walter, S, Vivot, A, Tchetgen, EJTchetgen, Kawachi, I, M. Glymour, M
JournalAlzheimer Dis Assoc Disord
Date Published2016 Jul-Sep
ISSN Number1546-4156
KeywordsAfrican Americans, Alzheimer disease, Ethnic Groups, European Continental Ancestry Group, Female, Follow-Up Studies, Genome-Wide Association Study, Humans, Male, Memory Disorders, Middle Aged, Risk Factors, United States

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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Endnote Keywords

Gene Ontology/Diseases/Genes/Proteins

Endnote ID


Alternate JournalAlzheimer Dis Assoc Disord
Citation Key6498
PubMed ID26756387
PubMed Central IDPMC4940299
Grant ListP30 AG015272 / AG / NIA NIH HHS / United States
R01 AI104459 / AI / NIAID NIH HHS / United States
T32 NS048005 / NS / NINDS NIH HHS / United States