Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality

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Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality

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Title: Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality
Author: Mez, Jesse; Marden, Jessica R. ORCID  0000-0001-9108-8711 ; Mukherjee, Shubhabrata; Walter, Stefan; Gibbons, Laura E.; Gross, Alden L.; Zahodne, Laura B.; Gilsanz, Paola; Brewster, Paul; Nho, Kwangsik; Crane, Paul K.; Larson, Eric B.; Glymour, M. Maria

Note: Order does not necessarily reflect citation order of authors.

Citation: Mez, 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.
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Abstract: Introduction: 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.
Published Version: doi:10.1016/j.dadm.2017.07.002
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604953/pdf/
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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492485
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