Alzheimer's & dementia (Amsterdam, Netherlands) · 2017
Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality.
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Mez Jesse, Marden Jessica R, 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
Аннотация
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.
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.