Validation of a polygenic risk score for dementia in black and white individuals

Jessica R Marden, Stefan Walter, Eric J Tchetgen Tchetgen, Ichiro Kawachi, M Maria Glymour, Jessica R Marden, Stefan Walter, Eric J Tchetgen Tchetgen, Ichiro Kawachi, M Maria Glymour

Abstract

Objective: To determine whether a polygenic risk score for Alzheimer's disease (AD) predicts dementia probability and memory functioning in non-Hispanic black (NHB) and non-Hispanic white (NHW) participants from a sample not used in previous genome-wide association studies.

Methods: Non-Hispanic white and NHB Health and Retirement Study (HRS) participants provided genetic information and either a composite memory score (n = 10,401) or a dementia probability score (n = 7690). Dementia probability score was estimated for participants' age 65+ from 2006 to 2010, while memory score was available for participants age 50+. We calculated AD genetic risk scores (AD-GRS) based on 10 polymorphisms confirmed to predict AD, weighting alleles by beta coefficients reported in AlzGene meta-analyses. We used pooled logistic regression to estimate the association of the AD-GRS with dementia probability and generalized linear models to estimate its effect on memory score.

Results: Each 0.10 unit change in the AD-GRS was associated with larger relative effects on dementia among NHW aged 65+ (OR = 2.22; 95% CI: 1.79, 2.74; P < 0.001) than NHB (OR=1.33; 95% CI: 1.00, 1.77; P = 0.047), although additive effect estimates were similar. Each 0.10 unit change in the AD-GRS was associated with a -0.07 (95% CI: -0.09, -0.05; P < 0.001) SD difference in memory score among NHW aged 50+, but no significant differences among NHB (β = -0.01; 95% CI: -0.04, 0.01; P = 0.546). [Correction added on 29 July 2014, after first online publication: confidence intervalshave been amended.] The estimated effect of the GRS was significantly smaller among NHB than NHW (P < 0.05) for both outcomes.

Conclusion: This analysis provides evidence for differential relative effects of the GRS on dementia probability and memory score among NHW and NHB in a new, national data set.

Keywords: Dementia; genetics; race.

Figures

Figure 1
Figure 1
Histograms of the distribution of the genetic risk score with and without APOE among non-Hispanic whites and blacks. (A) Distribution of the AD-GRS including APOE among NHW (mean = 0.09, SD = 0.03). (B) Distribution of the AD-GRS excluding APOE among NHW (mean = 0.09, SD = 0.02). (C) Distribution of the AD-GRS including APOE among NHB (mean = 0.12, SD = 0.05). (D) Distribution of the AD-GRS excluding APOE among NHB (mean = 0.12, SD = 0.03).

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