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

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.