@article {6498, title = {Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.}, journal = {Alzheimer Dis Assoc Disord}, volume = {30}, year = {2016}, month = {2016 Jul-Sep}, pages = {195-202}, 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.

}, keywords = {Alzheimer disease, Black or African American, ethnicity, Female, Follow-Up Studies, Genome-Wide Association Study, Humans, Male, Memory Disorders, Middle Aged, Risk Factors, United States, White People}, issn = {1546-4156}, doi = {10.1097/WAD.0000000000000137}, author = {Jessica R Marden and Elizabeth R Mayeda and Stefan Walter and Vivot, Alexandre and Tchetgen Tchetgen, Eric J and Ichiro Kawachi and M. Maria Glymour} }