title: Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.
abstract: 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.
authors.affiliation: Departments of *Social and Behavioral Sciences §Biostatistics ∥Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA †Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA ‡INSERM U1153, Hôtel-Dieu Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Marden
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Mayeda
authors.forename: Stefan
authors.initials: S
authors.lastname: Walter
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vivot
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Tchetgen Tchetgen
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawachi
authors.forename: M Maria
authors.initials: MM
authors.lastname: Glymour
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors; D014481:United States; D044465:White People / Q000235:genetics*