title: Validation of a polygenic risk score for dementia in black and white individuals.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health 677 Huntington Ave, Boston, Massachusetts, 02115.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Marden
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health 677 Huntington Ave, Boston, Massachusetts, 02115 ; Department of Epidemiology and Biostatistics, University of California at San Francisco San Francisco, California.
authors.forename: Stefan
authors.initials: S
authors.lastname: Walter
authors.affiliation: Department of Biostatistics, Harvard School of Public Health 677 Huntington Ave, Boston, Massachusetts, 02115 ; Department of Epidemiology, Harvard School of Public Health 677 Huntington Ave, Boston, Massachusetts, 02115.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Tchetgen Tchetgen
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health 677 Huntington Ave, Boston, Massachusetts, 02115.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawachi
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health 677 Huntington Ave, Boston, Massachusetts, 02115 ; Department of Epidemiology and Biostatistics, University of California at San Francisco San Francisco, California.
authors.forename: M Maria
authors.initials: MM
authors.lastname: Glymour
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000592:standards; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States; D044465:White People / Q000235:genetics
keywords: Dementia; genetics; race