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

TitleValidation of a polygenic risk score for dementia in black and white individuals.
Publication TypeJournal Article
Year of Publication2014
AuthorsMarden, JR, Walter, S, Tchetgen Tchetgen, EJ, Kawachi, I, M. Glymour, M
JournalBrain Behav
Date Published2014 Sep
ISSN Number2162-3279
KeywordsAfrican Americans, Aged, Aged, 80 and over, Dementia, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Genetic, Reproducibility of Results, Risk Assessment, Risk Factors, Surveys and Questionnaires, United States

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.

User Guide Notes

Alternate JournalBrain Behav
Citation Key8613
PubMed ID25328845
PubMed Central IDPMC4107377
Grant ListR01 AI104459 / AI / NIAID NIH HHS / United States
R01 ES020337 / ES / NIEHS NIH HHS / United States
T32 NS048005 / NS / NINDS NIH HHS / United States
AG03438501 / AG / NIA NIH HHS / United States