Polygenic risk and hazard scores for Alzheimer's disease prediction.

Genome-wide association studies (GWAS) have identified over 30 susceptibility loci associated with Alzheimer's disease (AD). Using AD GWAS data from the International Genomics of Alzheimer's Project (IGAP), Polygenic Risk Score (PRS) was successfully applied to predict life time risk of AD development. A recently introduced Polygenic Hazard Score (PHS) is able to quantify individuals with age-specific genetic risk for AD. The aim of this study was to quantify the age-specific genetic risk for AD with PRS and compare the results generated by PRS with those from PHS. Quantification of individual differences in age-specific genetic risk for AD identified by the PRS, was performed with Cox Regression on 9903 (2626 cases and 7277 controls) individuals from the Genetic and Environmental Risk in Alzheimer's Disease consortium (GERAD). Polygenic Hazard Scores were generated for the same individuals. The age-specific genetic risk for AD identified by the PRS was compared with that generated by the PHS. This was repeated using varying SNPs Polygenic Risk Score significantly predicted the risk associated with age at AD onset when SNPs were preselected for association to AD at Both PRS and PHS can be used to predict an age-specific risk for developing AD. The PHS approach uses SNP effect sizes derived with the Cox Proportional Hazard Regression model. When SNPs were selected based upon AD GWAS case/control

Déclaration de conflit d'intérêts

JH‐grants from Cytox, outside the submitted work; JW‐patent for diagnostics on some SNPs identified as associated with AD; VE‐P – personal fees from Consultancy, outside the submitted work. GL, RS, MS, AF, PB, GS, and NF have nothing to report.