We re-investigated the effect of polygenic risk scores (PRS) and the polygenic hazard score (PHS) on various hallmarks of Alzheimer’s disease. We found that earlier reports of associations between PHS and amyloid were overestimated owing to incomplete correction for the effect of the APOE locus. Also the effect of PHS on cognitive decline was overestimated in the same way. After rigorous adjustment for the APOE locus (ε2 and ε4 allele count) and stratification by clinical diagnosis, we found that there were only weak associations between polygenic scores and amyloid pathology and cognition. However, an effect on CSF tau (and p-tau) was persistent. The results were summarized in a late-breaking abstract for AAIC 2019 (click here for the poster).
A paper summarizing these results has been recently published in Brain Communications.