We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Validation of a polygenic risk score for dementia in black and white individuals.
- Authors
Marden, Jessica R.; Walter, Stefan; Tchetgen Tchetgen, Eric J.; Kawachi, Ichiro; Glymour, M. Maria
- 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 intervals have 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.
- Subjects
DEMENTIA; ALZHEIMER'S disease; META-analysis; GENOMES; CONFIDENCE intervals
- Publication
Brain & Behavior, 2014, Vol 4, Issue 5, p687
- ISSN
2162-3279
- Publication type
Article
- DOI
10.1002/brb3.248