Mez, JesseMarden, Jessica RachelMukherjee, ShubhabrataWalter, StefanGibbons, Laura E.Gross, Alden L.Zahodne, Laura B.Gilsanz, PaolaBrewster, PaulNho, KwangsikCrane, Paul K.Larson, Eric B.Glymour, M. Maria2017-12-062017Mez, J., J. R. Marden, S. Mukherjee, S. Walter, L. E. Gibbons, A. L. Gross, L. B. Zahodne, et al. 2017. “Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality.” Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring 8 (1): 188-195. doi:10.1016/j.dadm.2017.07.002. http://dx.doi.org/10.1016/j.dadm.2017.07.002.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492485Introduction: We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. Methods: We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. Results: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00–1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41–1.00, P = .05). Discussion Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.en-USAlzheimer's diseaseLongevityMortalitySurvival analysisGenetic risk scoreSelection biasCollider stratification biasSurvivor biasGenome-wide association study (GWAS)Adult Changes in Thought (ACT)Health and Retirement Study (HRS)Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)Journal Article2017-12-0610.1016/j.dadm.2017.07.002