NG00099 - Results of gene - based weighted burden analyses using SCOREASSOC and GENEVARASSOC and multivariate analyses of variants near APOE applied to the ADSP Discovery Case - Control Based Extension Study.

In this study 3000 whole genome sequenced cases and controls with different ancestries from the Alzheimer's Disease Sequencing Project were subjected to gene-based weighted burden analysis to identify risk genes. Additionally, individual variants in the APOE region were tested for association with LOAD. When using the APOE variants as covariates no individual genes showed statistically significant evidence for association after Bonferroni correction for multiple testing. Likewise, for those variants initially showing evidence of association with LOAD incorporating the APOE variants as covariates dramatically reduced the strength of association. These results demonstrate that the differential association of APOE across ancestries is not driven by another variant in the region. It seems likely that no other variants in the region have a direct effect on LOAD risk.