Fig. 1: An illustration of the workflow of deriving polygenic resilience scores for late-onset Alzheimer’s disease (LOAD) for design 1 and design 2.
From: Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease
Stage 1: Using prior LOAD genome-wide association study (GWAS) results to calculate polygenic risk scores (PRSs). Stage 2: Identifying resilient individuals. In stage 2, we deployed two analysis designs differing in the definition of “resilient” individuals. In design 1, normal controls with LOAD PRSs ≥90th percentile were defined as “resilient” participants. In design 2, within the subset of normal controls who had at least one apolipoprotein E (APOE)-ε4 allele, a threshold of ≥80th percentile of PRSs (excluding SNPs in the APOE region) was used to define high-risk controls as “resilient”. Stage 3: Resilience GWAS and replication of polygenic resilience scores. GWAS was performed using “resilient” individuals and risk-matched affected cases from each of the two designs. For each design, polygenic resilience scores were derived and evaluated in external replication datasets. LD linkage disequilibrium, OR odds ratio, SNPs single-nucleotide polymorphisms.
