IC‐P‐173: EFFECTS OF NEWLY IDENTIFIED TOP AD CANDIDATE GENES ON MEMORY PERFORMANCE: SNP, GENE, AND EPISTASIS ANALYSES IN ADNI

interaction (PPI) database, and performed an epistasis analysis of the RAVLT-Total score.Methods:Genotype data of 1142 non-Hispanic Caucasian participants fromADNI-1 and ADNI-GO/2 [1] were downloaded, quality controlled, imputed to the Illumina 610Quad and OmniExpress platforms,and combined. PPI pairs were downloaded from Human Protein Reference Database (HPRD) [2]. SNPs within 8495 genotyped genes (6 10kb) were extracted (N1⁄4225,290) and around 35 million interactions among them were evaluated based on the HPRD protein interactions. Epistasis effect associated with b aseline RAVLT-Total score was examined with sex, age, education and handedness as covariates (INTERSNP [3]). Metacore enrichment analysis was performed on the identified genes. Results: At the significance level of p 1e6, 31 SNP interactions were associated with the RAVLT-Total score, corresponding to 13 known PPIs in HPRD database (Fig. 1). The effect of top interaction between AFAP1 and SRC was consistent in ADNI1 (p 1e-6), ADNI2/GO (p1⁄40.005), and their combination (p 1e-6). This interaction explained 4% variance of the RAVLT score on top of APOE and covariates. Enrichment analysis on 25 identified genes yielded several significant pathways shown in Table 1 (e.g., immune