Fig. 3

Association of the AD PRSsum with changes in cognitive functions. PRSsum was constructed as the unweighted sum of 5 standardized PRSs, each based on a separate GWAS described in Table 1. For each GWAS, the PRS were selected based on optimizing the coefficient of variation across 4 independent subsets of the SOL-INCA dataset. The figure provides the estimated effect size (beta) and 95% confidence intervals in the association of AD PRSsum with change in cognitive function from the baseline HCHS/SOL visit to the SOL-INCA exam. We provide results from three cognitive tests (digit symbol substitution, Brief Spanish English verbal learning tests (SEVLT), and word frequency, as well as from a change in a global measure of cognitive function, G-factor, computed based on the same tests. These phenotypes are described in the Supplementary Information. Effect estimates were obtained from linear mixed model implemented in the GENESIS R package, accounting for genetic relatedness, household, and block unit sharing via random effects, and adjusted for age at the HCHS/SOL baseline exam, time between exams, sex, study center, education level, APOE allele counts, and the first 5 principal components of genetic data as fixed effects. The sample sizes used for analyses in this figure ranged from n = 4,037 to n = 4,613. See Supplementary Table 5 for accurate numbers for each analysis